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A Framework for Drug Regulatory Authority
Submitted to
Ministry of Health
Government of Pakistan
By
Sarfaraz K. Niazi, Ph.D.
Consultant to the Ministry of Health,
Government of Pakistan
Table of Content
Drug Regulatory Authority Framework .................................................................................... 3
Purpose of this Document ...................................................................................................... 3
Source of this Document ....................................................................................................... 3
History of Project ................................................................................................................... 3
Strategy for Establishment of Drug Regulatory Authority Plan ............................................ 5
Background Issues ................................................................................................................. 7
The Country ....................................................................................................................... 7
International Healthcare..................................................................................................... 7
Present System of Enforcing Drug Act 1976 ........................................................................ 8
Current Human Resource for Drug Control within the MOH ............................................... 9
Top Level Issues .................................................................................................................. 10
Macro-level Issues and Their Solutions (to form part of DRA rules and policies) ............. 16
Proposed Regulatory System ............................................................................................... 31
Legal Status: .................................................................................................................... 31
Vision Statement:............................................................................................................. 31
Mission Statement: .......................................................................................................... 31
Objectives: ....................................................................................................................... 31
Powers: ............................................................................................................................ 32
Human Resource Requirements: ..................................................................................... 32
Administrative Structure of DRA ........................................................................................ 40
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Drug Regulatory Authority Framework
Purpose of this Document
This document is intended to outline the proposed strategic positioning for the establishment of a
Dug Regulatory Authority (hereinafter referred to as DRA) and present a draft of an Act to
establish DRA in Pakistan. This document may be distributed to stakeholders for their comments.
The final document will then be redrafted for submission to the Cabinet Division for further action.
Source of this Document
This document is prepared by Dr. Sarfaraz K. Niazi, a consultant to the Ministry of Health. Dr.
Sarfaraz K. Niazi is a Foreign Professor at HEJ Research Institute, an Adjunct Professor at
University of Houston, Houston, Texas and a Patent Agent (US Patent and Trademark Office,
Washington, DC), and has over 35 years of experience in pharmaceutical manufacturing, working
with worldwide regulatory authorities, securing regulatory approvals (FDA), offering consultation
to pharmaceutical and biotechnology companies worldwide, conducting pharmaceutical research
and teaching pharmaceutical sciences worldwide. He has authored several key text and reference
books on the subject of pharmaceutical and biopharmaceutical products manufacturing and
regulatory compliance and owns several US patents for his inventions.
History of Project
1. The Economic Coordination Committee (ECC) while considering the Summary dated 4
October 2002, submitted by the Ministry of Industries and Production, on Implementation of
Industrial Policy for Pharmaceutical Sector, directed the Ministry of Health to establish a Drug
Regulatory Authority (DRA) within a year to provide an institutional mechanism for regulating
the pharmaceutical industry in the country. The cabinet in its meeting held on 16 October 2002
endorsed the decision of the ECC.
2. The Ministry of Health requested the WHO to arrange an international consultant to review the
existing system and highlight models of drug regulations in the region and globally and propose
a Drug Regulatory Authority framework for Pakistan. The WHO constituted a panel, which
submitted its interim report to the WHO. A two-member WHO Technical Advisory Mission,
who visited Pakistan in December 2003 for the purpose, examined the interim report prepared
by that panel, and held meetings with the officials in the Ministry of Health at Islamabad and
the provincial governments. The WHO Technical Advisory Mission made the following
recommendations:
MOH may take necessary steps to institutionalize the process of national drug policy
formulation, implementation, monitoring and evaluation. A small policy and planning
unit may be established for this activity.
MOH may initiate a national debate to review the National Drug Policy document and
formulate the National Master Strategy Plan for policy implementation.
MOH may develop and implement a national plan for Drug Information System to
computerize Drug Registration, Licensing and other pharmaceutical related record.
Adopt national system approach in developing National Drug Quality Assurance
mechanisms, for quality evaluation of drugs, vaccines, biologics, veterinary, food
supplements, and other products.
Intensive training be imparted to inspectors on the GMP so as to enable them to develop
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SOPs for all kinds of inspections. Inspection frequency may be correlated to the GMP
implementation status.
Capacity-building of laboratories to run all necessary quality tests.
Develop SOPs and policies for the post marketing surveillance of drug products all over
the country.
The setup recommended for Pakistan at this stage for a Drug Regulatory Authority is an
“An authority which is technically, administratively and financially autonomous, but
working under the Ministry of Health.”
Develop and implement a national plan for up-grading Federal and Provincial facilities
and Human Resource Development in the area of Drug Quality Assurance.
Organize a meeting in MOH to develop and elaborate pricing system in Pakistan.
Serious measure to be taken to increase public budget for essential medicines. The
support from Zakat and Ushr should be encouraged in this respect.
A national system be developed in the areas of: (i) Essential Drug Lists for various
health facilities; (ii) national use of drugs; and (ii) good management of drug supply.
3. The above recommendations were subsequently shared informally with the Management
Services Wing of the Establishment Division, which was of the view that under rule 68 of the
“Secretariat Instructions” it was obligatory on all the Ministries/Divisions to refer the
cases/proposals of restructuring/reorganization/creation of a new organization/expansion, etc.,
to the MS Wing for consultation/technical evaluation. A final report is still awaited from the
WHO.
4. In May 2004, the Ministry of Health established a Committee to write the objectives, functions
and tasks to be performed by DRA and in June 2004 the Management Services Wing of
Establishment division conducted a study on establishment of DRA and submits report on 23rd
October 2004. In October 2005 the Ministry of Health requested from the Higher Education
Commission, the services of Dr. Sarfaraz K. Niazi, currently serving as Foreign Professor at the
HEJ Research Institute to summarize, analyze and make recommendations on a draft of DRA
Act to the Ministry of Health no later than end of December 2005. Dr. Niazi submitted a draft
to the Secretary Health in the first week of January 2006.
5. On 27 December, 2005, the WHO submitted a report to the MOH on “Establishing Drug
Regulatory Authority in Pakistan: WHO‟s Mission Report prepared by a committee comprising
Dr. Zafar Mirza (Regional Advisor, Essential Drugs and Biologicals, EMRO/WHO, Cairo,
Egypt), Ms. Eishah Binti A. Rahman (Deputy Director Drug Evaluation and Safety Division,
National Pharmaceutical Control Bureau, Ministry of Health, Malaysia) and Ms. Yuawadee
Patanawong (Director Thailand FDA, Ministry of Public Health). A copy of this report was
provided to Dr. Niazi in February 2005. Given below are the highlights of the recommendations
in the report:
The mission of the DRA is “To protect and promote public health by ensuring equitable
access to safe, efficacious, quality and affordable medicines and other selected health
products and their rational use through implementation of National Medicines Policy
and effective enforcement of relevant legislation.”
The scope and coverage of the DRA proposed to include, at least in the beginning,
medicines for human use including synthetic pharmaceuticals, vaccines and other
biologicals; blood products, pharmaceutical raw materials; herbal medicines;
homeopathic medicines; medicines for veterinary use; pesticides and medical devices.
The authority is proposed to be of 6 members and a Chairman who would be the head of
the authority. The other six members are: Member National Medicines Policy and
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Research, member Licensing and Quality Assurance, member Product Evaluation and
Registration, member, Traditional Medicine Policy and Regulation, member Medical
Device Regulation and Member, Finance and Administration.
The DRA Policy Board shall be chaired the Minister of Health and Chairman DRA shall
be the Secretary; there will be 16 other members including federal secretaries of health;
Commerce; Industries and Production; federal Director General Health; two imminent
physicians; two imminent pharmacists; 4 provincial secretaries of health; one
representative of a national consumer organization.
The DRA will be organized in six different departments headed by a director; five
cadres of personnel are recommended: Chairman and Members, Directors,
Coordinators, Officers and Assistants.
The six directorates recommended include:
i. Department of National Policy and Research with four subunits: National
Medicines Policy Unite, Medicine Prices Unit, Rational Use of medicines unit,
National Poisoning Information Center (in collaboration with a university or
hospital).
ii. Department of Licensing and Quality Assurance: consisting of two subunits
Licensing and GMP Unit, Quality Labs and Testing.
iii. Department of Product Evaluation and Registration: Medicines Registration
Unit, Biologicals Control, Medicines Promotional Control.
iv. Department of Traditional Medicine Policy and Registration: Traditional
Medicine Policy, Unani tibb, Homeopathy.
v. Department of Medical Device Regulation: Medical devices approval and
registration, Health Technology assessment.
vi. Department of Finance and Administration: Finance, HRD, Administration.
A total headcount of 100 and 18 federal drug inspectors is proposed; for comparison
purpose the Thailand FDA has 518 financially supported staff.
The DRA is projected to be autonomous and financially self-sufficient; clear warning is
provided in raising funds from the pharmaceutical industry.
An Act will be required for ratification by the Parliament to form it into a law.
6. In November 2005, Dr. Sarfaraz K. Niazi presented an overview of the proposed framework for
DRA to the Ministry of Health in a meeting chaired by the Secretary Health; Dr. Niazi was then
instructed by the Secretary, Health to complete the task of writing a framework for DRA, as
presented in this document.
7. On 14th February 2006, Dr. Niazi presented a draft of the DRA structure to the Minister of
Health and the Secretary Health and detailed discussions were held with the MOH senior staff
and appropriate changes made to the document.
Strategy for Establishment of Drug Regulatory Authority Plan
This plan presented in this document is a crucial exercise that will have significant long-term
impact on the healthcare system of Pakistan. As a result, prior to suggesting a mechanism to
regulate drugs in Pakistan, a historic, philosophic and sociologic discussion on the need for
proposed reorganization is also presented. Most important is the exercise that would first identify
current issues, problems and predicaments and then offer a plausible and practical resolution. It is
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only when all issues related to drug regulation are fully resolved that a foundation of a new agency
can be laid since the structure of the agency will be dependent on the functions it is supposed to
perform. In designing a structure for the DRA, a zero-based strategy is adopted; through this
strategy, a structured approach is taken to identify manpower and resources assuming and goes
through following steps:
Write out
Vision
Statement
Write out
Mission
Statement
Write out
Objectives
Write out
Funcions
Define
manpower
requirement
Define facility
requirement
Create
Budget
In creating a strategy for DRA, therefore, no assumptions are made on the existing systems, the
intent being to fill positions with qualified individuals and not to insert available manpower into
created slots. It is anticipated that a large number of current staff involved in drug regulation will be
slotted in the proposed system.
6
Background Issues
The Country
Pakistan has current population of 162 million growing at a rate of over 2% per annum making it
the fifth largest country in the world. With the low literacy rate of around 30% and with over one-
third of the population falling below the official poverty line it is not surprising that Pakistan has
one of the highest infant mortality rates in the world. The life expectancy at birth is around 63
years. (CIA World Factbook 2005 http://www.cia.gov/cia/publications/factbook/). Fortunately, the
economic recovery in Pakistan is robust with around 6% real GDP growth and per capita income of
around $2,200 [CIA World Factbook]. The annual GDP of Pakistan stands at around $370B of
which less than one billion is spent on pharmaceutical purchases (not included traditional
medicines) that account for expenditure of less than one-third of one percent of GDP, one of the
lowest in the world. This is contrasted with the highest expenditure made in the US where full 2.5%
of GDP goes toward pharmaceutical purchases (around $300B). The average per capita yearly
expenditure in Pakistan is around $5.50 or Rs. 350/yr. However, these numbers could not be
extrapolated as generalized because of the great dichotomy in the distribution of per capita GDP,
high cost of treatment of diseases in the poverty-ridden populations, irrational prescribing trends,
etc., As a result, even though the total expenditure on drugs is not large, the affordability of safe
and effective medications remains one of the most serious problems facing the country.
International Healthcare
The World Health Organization has long emphasized the approach that access to drug, whether in
developed or developing countries, is reliant on four interlocking factors:
Rational selection of the drug to be used,
Affordable prices for those drug,
Sustainable financing of healthcare (including drug) and
Reliable health and supply systems. An effective drug regulatory authority (DRA) is a
crucial part of a “reliable health and supply system.” Whereas consideration of affordable
prices is generally not taken under direct purview of the DRA, it is essentially controlled
and governed by DRA. It is remarkable that the WHO considers the use of “affordable”
rather than “cheap” to assure that substandard cheap drugs do not enter the commerce and
instead emphasis is placed on rationalization of prices coupled with support systems to
make drugs affordable
Drug registration is the process by which a national or regional DRA approves the use of a
medicine in a particular country, having considered evidence of the drug‟s safety, quality and
efficacy. It is thus primarily concerned with protecting public health. However, where drug
regulatory processes are unwieldy and delay entry of needed drug in a particular market, they can
be seen as a barrier to access as well as to profits and the growth of the pharmaceutical industry.
Pre-marketing assessment of safety, quality and efficacy is however only one component of a drug
regulatory system. In addition, attention must be paid to ongoing assessment and inspection of the
entire pharmaceutical supply chain (including manufacturers, importers, exporters, wholesalers,
distributors and final sellers), maintenance of a register of approved products and post-marketing
surveillance (including random quality checks and pharmacovigilance systems), control over the
promotion and advertising of drug and the provision of drug information. Lastly, there is a view
that issues related to the rational pricing of drug and considerations of cost-effectiveness may also
legitimately fall within the ambit of the drug regulatory agency.
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Developing countries face considerable challenges in ensuring greater access to drug, yet also
ensuring that the drug that are available are safe, of acceptable quality and efficacious. While often
under-resourced and poorly equipped to assess increasingly complex data, their DRAs are expected
to register drug more quickly and at the lowest possible cost. They must decide how to handle
applications for new chemical entities (NCEs), interchangeable multi-source drug (IMMs, also
referred to as “generics”), new fixed-dose combination products (FDCs) and even traditional or
complementary drug. New chemical entities are novel molecules developed by researchers and
subject to patent protection for a limited period of time. Once the patent expires (or a license is
issued), copies of the medicine may legally be made. These are termed multi-source drug and
should in most cases be interchangeable with the original medicine. Regulators must also acquire
the relevant technical expertise and organize their processes in order to facilitate the use of to use
flexibilities in international trade agreements to improve access to drug, such as compulsory
licensing and parallel importation. In addition to these global issues and consensus thereof, some
issues are of domestic origin. These include an increasing demand by the Government to create
transparent governance systems, improved efficiencies and enhanced affordability of drugs to the
Pakistani population. All of these issues need to be addressed and a tentative resolution adopted
since this will greatly determine the nature, the size and the role of the proposed DRA in Pakistan.
As an ancillary note, it is important to recognize that whereas the proposed DRA will deal mainly
with the regulation of drugs, an equally important problem is the issue of food, which is responsible
for the greatest contribution to the high infant mortality, wide variety of infectious diseases and the
smaller life expectancy of the Pakistani population. The agenda of the world‟s largest and most
effective regulatory authority, Food and Drug Administration is to protect and advance the health of
Americans, “by ensuring the safety and security of food, medical products and animal drugs and
feed while promoting innovation so that consumers may rapidly obtain more effective health-care
products and information.” In year 2006, the US will spend around $2 Billion to perform this
function. It is important to note that the first priority of the FDA is to protect human health and
what they consider most important is the quality of food and drugs in that order. At some time in
the future, after the DRA has been established and effective in delivering its mission, the MOH is
requested to consider expanding the role of DRA into FDRA to encompass control of food as well.
Present System of Enforcing Drug Act 1976
The drug regulation finds a place in the Concurrent Legislative List Section 20 given in the further
schedule of the 1973 Constitution of Islamic Republic of Pakistan. In exercise of powers conferred
upon the Federal Government by the aforesaid provision of Constitution, and Act entitled “Drugs
Act, 1976” was promulgated to regulate the import, export, manufacture, storage, distribution and
sale of drugs. Under this Act, the function to regulate: (i) import and export; (ii) manufacturing
through Central Licensing Board (iii) registration through Drug Registration Board; and (iv) Price
fixation, have assigned to the Drugs Control Organization of the Ministry of Health, and the
functions to regulate sale of drugs through the Provincial Quality Control Boards have assigned to
the provincial governments.
At the federal level, the administration and enforcement of the Drugs Act, 1976 is carried out by the
Drugs Control Organization of the Ministry of Health. Given below is a distribution of current
approved human resources:
Location Headcount
Ministry of Health, 162
Islamabad
FID, Islamabad 8
DCA Lahore, Islamabad 39
8
DCA Peshawar 17
DCA Quetta 12
DCA Karachi 40
FID Hyderabad 7
CDL Karachi 74
NCL Islamabad 11
TOTAL 370
The distribution of the current staff of Drug Control Organization is given below:
80
75
70
65
60
55
50
Headcount
45
40
35
30
25
20
15
10
5
0
21 20 19 18 17 16 15 12 11 10 9 8 7 6 5 4 2 1
Grade
Current Human Resource for Drug Control within the MOH
Grade Headcount Positions
21 2 Chief Drug Controller
20 3 Drugs Controller, Cost Accountant
19 9 Deputy Director General, Chair QC
18 25 Deputy Drugs Controller, Assistant Director General
17 30 Assistant Drugs Controller 11, Programmer, Private Secretary, Staff
Officer
16 5 Assistant Chemist, Superintendent
15 22 Stenographer, Assistant In Charge
12 29 Stenotypist, computer operator
9
11 39 Assistant
10 13 Technical Assistant
9 7 Senior Technicians
8 2 Accountant, Head Clerk
7 13 Upper division clerk
6 2 Technicians
5 51 Lower division clerk, Lab Assistant
4 21 Driver, DMO
2 17 Daftary, Lab Attendant
1 78 Naib Qasid, Chowkidar, Laborer
Top Level Issues
The broad level issues as discussed below provide a framework to create DRA:
Issue Debate
Should developing Developing country regulators are often under-resourced and lack
country regulators access to the high levels of scientific expertise needed for the
build their own effective assessment of registration dossiers for new chemical
capacity or rely on entities (NCEs) and interchangeable multi-source drug (IMMS, or
regional efforts or „generics‟). It has been argued that:
even larger regulators
It is better for developing countries to rely on the assessments
in developed
of major drug regulatory authorities, such as those in the US
countries?
and Europe, when faced with an application for registration
of an NCE.
Regional cooperation is needed when considering
applications for IMMs, as the needed expertise is also in
short supply.
In specific areas, the WHO pre-qualification program may assist
developing countries. NCE dossiers are generally assessed by the US
and European authorities. Their assessments could therefore be
relied upon by developing countries as sufficient proof of safety,
quality and efficacy. Applications for interchangeable multi-source
drug (IMMs) may be specific to developing countries, perhaps
depending on local patent status and law or local manufacturers.
However, they also demand expertise that is in short supply.
Regional cooperation may allow scarce expertise to be more
efficiently applied. However, inspection of manufacturing plants
may still be necessary, especially if products are made only for
export. A particular challenge is the consideration of applications to
register fixed-dose combinations (FDCs). There have been keen
debates on which types of data are needed for a particular
combination. In some specific areas (HIV/AIDS, TB, malaria), the
WHO pre-qualification project may be relied upon by countries
without access to a competent MRA, but this needs to be clearly
10
differentiated from the WHO Certification Scheme on the Quality of
Pharmaceutical Products Moving in International Commerce. One of
the ways in which resources have been shared has been through the
Pharmaceutical Inspection Convention and the Pharmaceutical
Inspection Cooperation Scheme (PIC/S). Membership of the PIC/S is
seen as evidence of a DRA being “stringent”. Pakistan is not a
member of this organization.
How should drug Funding regulatory systems and retaining suitably qualified staff is a
regulatory systems be challenge in all settings. However, if a system is developed wherein
funded and how those functions that require high cost to perform, the DRA in
should their Pakistan can be fully funded by user fees. Similar fees are charged
performance be by the agencies like the FDA, though in US, these fees contribute
assessed? only about 50% of the cost of review. Reliance on user fees as a
funding source may make regulators more likely to see
pharmaceutical manufacturers as the constituency to which they are
primarily responsible, rather than the public. This may also bias their
views on the reliability of industry-supplied data. Other measures of
performance, accountability and transparency should be stringently
applied. It is anticipated that a sum of Rs. 100 Million is available
per year for the purpose of managing DRA and that this amount be
easily doubled with appropriate fee enhancement. It is noteworthy
that a fee structure should take into account not just the dossier
review but all inquiries related to registration of drugs. Generally,
pharmaceutical manufacturers are not unduly burdened by these fees
and the argument goes that if they can not pay these fees, what are
the chances that they will be able to afford other expenses related to
the quality of products. Therefore, in the proposed system, it is
suggested that the DRA should be a totally self-financing authority;
there may however, be an interim period when the support of
Government may be required in the initial phases.
What impact would The International Conference on Harmonization (ICH) has sought to
“harmonization” have improve the efficiency of drug registration in the US, Europe and
on developing Japan by creating common templates and standards. Regional
country regulators? harmonization has also been achieved in Europe, with procedures for
reciprocal and mutual recognition of decisions. The WHO has also
been active in setting standards at the international level. It has been
argued that:
Applying ICH standards and processes to non-ICH countries
will increase costs and hamper access to necessary drug,
particularly IMMs.
WHO is the more appropriate intergovernmental organization
to set international standards.
Regional efforts are difficult to arrange and may result in the
domination of the area by the strongest regulator involved.
The ICH process has made some useful contributions, such as the
Common Technical Document (CTD) standard for trial reports.
Using this format avoids the unnecessary costs of reformatting
submissions for each country in which registration is sought. It is of
greatest use when preparing NCE applications. However, a far
greater problem is faced in harmonizing requirements for IMM
11
(generic) registration.
There are considerable challenges facing smaller DRAs that lack the
technical expertise necessary to decide when bioequivalence data are
needed and how to assess such data when they are presented.
Generally, there is no solid evidence that adopting ICH guidelines
would allow the DRA to operate more efficiently. As a result, the
DRA will, at least in the near future, rely more on the WHO
guidelines and adopt these and where necessary from other
regulatory authorities as needed.
One of the most important considerations here is the option to write
its own guidelines. Regulatory authorities take often years and spend
millions of dollars in expert reviews and debates prior to finalizing
guidelines. Periodic revisions keep the content updated and that adds
additional costs. The DRA proposed here should not attempt to
rewrite these guidelines and instead refer to them where they are
desired. Historically, the MOH has rewritten WHO and ICH
guidelines only to find that these are obsolete, erroneous and raising
questions about their validity.
How do intellectual Completely different laws and regulatory authorities usually govern
property rights and drug regulatory issues and intellectual property rights. However, the
drug regulation extension of a single standard of intellectual property right protection
interface and affect to all inventions (including drug) and its application to all countries
access to drug? that are signatories to the agreements that created the World Trade
Organization (WTO) has created new barriers to access to essential
drug. These barriers have been recognized and their potential impact
on public health acknowledged, and in response, important
flexibilities in respect of the Agreement on Trade Related
Intellectual Property Rights (TRIPS) can be exploited by developing
countries. Two of these are compulsory licensing and parallel
importation. However, it has been argued that an effective national
DRA must be in place to allow for the effective operation of
compulsory licenses and parallel trade, since these two flexibilities
must generally be utilized at the country-level. If health, patent and
drug regulatory authorities are not working closely together, the
potential benefits of these flexibilities may not be realized.
It is important to stress that DRAs are not in the business of policing
patents, nor should their decisions be influenced by consideration of
the patent status of a product. This has been the case in many
settings, for example where so-called “Bolar” exceptions are used to
allow the submission of a dossier to the DRA prior to expiry of the
patent on that particular product and/or process. Although the
potential of the TRIPS “flexibilities” have been well described, there
is little actual evidence of their use in the field. There are however,
many ways in which a lack of coordinated action between health,
patent and drug regulatory authorities can delay access to a medicine
that is the subject of a compulsory license, a parallel importation
effort or which has to be imported into a non-producing country
from a producing country. Of great concern is the trend for bilateral
trade agreements between developed and developing countries to
include additional intellectual property protection beyond the
minima stipulated in the TRIPS Agreement. These include
12
provisions for data protection for a number of years after submission
to a DRA. In such cases, subsequent applications (for example for
IMMs) cannot be considered on the basis of access to or even mere
reliance upon the safety and efficacy data included in the initial
submission. To repeat such studies would be not only wasteful and
time-consuming but also potentially unethical. Finally, the impact of
China and India becoming TRIPS compliant has yet to be felt.
The DRA proposed here will include a large support function to
resolve intellectual property issues as in Pakistan most of the TRIPS
matters pertain to drugs. Since DRA will rarely review an NCE
submission, it is easier for the DRA to defer such considerations as
“Bolar” compliance and instead require drug manufacturers to
submit completed IMMs in line with the registration requirements as
stipulated in the Drug Act. Clear principles of accepting these
applications will be described; one such requirement will be a
certification by the applicant that the product proposed does not
violated any patents currently enforceable in Pakistan. This is a
similar system now in use by the FDA where the responsibility is
shifted to the applicant; through a system of informing all concerned
parties, validity of these claims is readily established without any
cost to DRA. Other issues like compulsory licensing will be handled
through in-house legal expertise.
For IMMS evaluation, the DRA shall accept credible public domain
studies to support safety and efficacy of drug products; this is in line
with accepted practices worldwide.
What Code of Good A well-defined Code of Good Regulatory Practice includes the
Regulatory Practice following essential components:
should be followed?
Efficiency
Adopt and maintain only regulations for which the costs on society
are justified by the benefits to society, and that achieve objectives at
lowest cost, taking into account alternative approaches to
regulation.
Efficiency Guidelines
Consideration of alternatives to regulation: regulatory design
should include an identification and assessment of the most
feasible regulatory and non-regulatory alternative(s) to
addressing the problem.
Minimum necessary regulation: when government
intervention is desirable, regulatory measures should be the
minimum required, and least distorting, in achieving desired
outcomes.
Regulatory benefits outweigh costs: in general, proposals
with the greatest net benefit to society should be selected and
implemented.
Reasonable compliance cost: the compliance burden imposed
on society by regulation should be reasonable and fair
compared to the expected regulatory benefit.
Minimal fiscal impact: regulators should develop regulatory
13
measures in a way that minimizes the financial impact of
administration and enforcement.
Minimal adverse impact on competition: regulation should be
designed to have a minimal negative impact on competition.
International compatibility: where appropriate, regulatory
measures or standards should be compatible with relevant
international or internationally accepted standards or
practices, in order to maximize the benefits of trade.
Effectiveness
Regulation should be designed to achieve the desired policy
outcome.
Effectiveness Guidelines
Reasonable compliance rate: A regulation is neither efficient
nor effective if it is not complied with or cannot be
effectively enforced. Regulatory measures should contain
compliance strategies which ensure the greatest degree of
compliance at the lowest possible cost to all parties. Incentive
effects should be made explicit in any regulatory proposal.
Compatibility with the general body of law, including the
statute which it amends, statutes which apply to it, and the
general body of the law of statutory interpretation.
Compliance with basic principles of our legal and
constitutional system, including the Drug Act 1976, the WTO
and TRIPS provisions.
Flexibility of regulation and standards: regulatory measures
should be capable of revision to enable them to be adjusted
and updated as circumstances change.
Performance-based requirements that specify outcomes
rather than inputs should be used, unless prescriptive
requirements are unavoidable. This will help ensure
predictability of regulatory outcomes and facilitate
innovation.
Review regulations systematically to ensure they continue to
meet their intended objectives efficiently and effectively.
Transparency
The regulation making process should be transparent to both the
decision-makers and those affected by regulation.
Transparency Guidelines
Problem adequately defined: identifying the nature and
extent of the problem is a key step in the process of
evaluating the need for government action. Properly done,
problem definition will itself suggest potential solutions and
eliminate others clearly not suitable.
Clear identification of the objective of regulation: the policy
goal should be clearly specified against the problem and have
14
a clear link to government policy.
Cost benefit analysis: regulatory proposals should be subject
to a systematic review of the costs and benefit. Resources
invested in cost benefit estimation should increase as the
potential impact of the regulation increases.
Risk assessment: regulatory proposals should be subject to a
risk assessment which should be as detailed as is appropriate
in the circumstances.
Public consultation should occur as widely as possible, given
the circumstances, in the policy development process. A
well-designed and implemented consultation program can
contribute to better quality regulations, identification of the
more effective alternatives, lower costs to business and
administration, ensure better compliance, and promote faster
regulatory responses to changing conditions.
Direct approaches to problem: In general, adopting a direct
approach aimed at the root cause of an identified problem
will ensure that a more effective and efficient outcome is
achieved, compared to an indirect response.
Clarity
Regulatory processes and requirements should be as
understandable and accessible as practicable.
Clarity Guidelines
Make things as simple as possible, but not simpler, in
achieving the regulatory objective.
Plain language drafting: where possible, regulatory
instruments should be drafted in plain language to improve
clarity and simplicity, to reduce uncertainty, and to enable
those affected to better understand the implications of
regulatory measures.
Discretion should be kept to a minimum, but be consistent
with the need for the system to be fair. Good regulation
should attempt to both minimize and standardize the exercise
of bureaucratic discretion, in order to reduce discrepancies
between government regulators, reduce uncertainty, and
lower compliance costs.
Educating the public as to their regulatory obligations is
fundamental in ensuring compliance.
Equity
Regulation should be fair and treat those affected equitably.
Equity Guidelines
Obligations, standards, and sanctions should be designed in
such a way that they can be imposed impartially and
consistently.
Regulation should be consistent with the principles of the
Bills and Acts promulgated by the Government and the
15
expectations of those affected by regulation, as to their legal
rights, should be met.
People in like situations should be treated in a similar
manner; similarly, people in disparate positions may be
treated differently.
Reliance should be placed on processes and procedures of
the regulatory system: a regulatory system is regarded as fair
or equitable when individuals agree on the rules of that
system, and any outcome of the system is considered just.
Macro-level Issues and Their Solutions (to form part of DRA rules and policies)
Issue Solution
General. The safety and efficacy of It is the intent of DRA to require all companies in
drugs manufactured in Pakistan can Pakistan to secure a third-party certification for its
be substantially improved if compliance to cGMP (current good manufacturing
pharmaceutical manufacturers practices). It is fully recognized that such compliance
licensed by the MOH are additionally can not be made through punitive measures alone.
required to upgrade their Use of the WHO Certification Scheme on the
manufacturing facilities. Whereas the Quality of Pharmaceutical Products Moving in
current system of inspection provides International Commerce WHO/DAP/94.21. World
some level of compliance, the fact Health Organization (1994) is recommended:
that no company in Pakistan has http://www.who.int/medicines/library/dap/who-dap-
received cGMP certification from any 94-21/who-dap-94-21.pdf
international body and is able to The WHO pre-qualification project
export drugs to regulated markets (http://mednet3.who.int/prequal/) provides access to
requires an inquiry into its causes. all of the relevant documents about the WHO pre-
The world is divided into four regions qualification program. It covers the assessment of
in terms of quality of pharmaceutical product dossiers containing data and information as
products: regulated (US, Japan, required in the guidelines, norms and standards of
Western Europe), semi-regulated the WHO, for safety, quality and efficacy; the
(Gulf, Southeast Asia, East Europe), assessment of manufacturers for compliance with
less regulated (China, South Asia, WHO Good Manufacturing Practices (GMP) and
Middle East) and unregulated (Many data verification; and the assessment of Contract
African countries). This classification Research Organizations (CROs) for compliance with
is based on the enforcement of Good Clinical Practices (GCP) and Good Laboratory
compliance and not on the presence Practices (GLP), and data verification.
of regulations. Since Pakistan
regulatory systems are not as To encourage companies to secure a third-party
stringently applied, the industry has certification, the DRA will designate such companies
not been able to through enforcement, as Class A Companies. An incentive package of
systems of compliance. price, registration priority and other such measures
will be developed for Class A companies. The
market forces will then drive the entire industry into
a voluntary compliance with the cGMP. This is an
incentive approach opposite to the punitive
approaches that often fail to produce long-term
16
results. To assure that Class A companies are also
producing good quality Essential Drugs, the
incentive package will require them to participate in
manufacturing both types of drugs.
Safety of drugs is the primary reason Whereas many issues related to safety of
for complying with GMP. In this manufactured drugs will be resolved through cGMP
regard, the weakest link of the chain compliance as listed above, there shall always
appears to be the design of remain a need to monitor this on an ongoing basis.
manufacturing facilities that do not There is also a need to educate the industry on the
assure segregation of drugs present and continuously evolving trends in cGMP;
manufactured. The existing standards to accomplish this, the cand any other such form to
of international regulatory agencies educate industry on a continuing basis. Equally
place the greatest emphasis on the use important, the role of the education unit will be train
of separate air-handling systems to drug inspectors and keep their knowledge current. It
totally isolate manufacturing will be important to assure that these teams are not
operations and additionally require reviewed as vigilance teams but friendly partners to
extensive cleaning validation—both the industry. The DRA may outsource part or all of
of these factors could not be the functions of education. DRA will participate in
implemented in most of the such programs as Pharmaceutical Inspection
manufacturing units currently Convention and the Pharmaceutical Inspection
operating in Pakistan. Cross Cooperation Scheme (PIC/S)
contamination of drugs produces http://www.picscheme.org/. The objective of the
extremely deleterious effects wherein PIC/S is: “to pursue and strengthen the cooperation
low level exposure to antibiotics, established between the participating authorities in
hormones and other immune system the field of inspection and related areas with a view
modulating compounds can produce to maintaining the mutual confidence and promoting
life-long effects on patients. The quality assurance of inspections, to provide the
MOH fully understands and framework for all necessary exchange of information
appreciates the severity and and experience, to coordinate mutual training for
seriousness of these flaws and has inspectors and for other technical experts in related
attempted to provide a partial solution fields, to continue common efforts towards the
by requiring drug companies to improvement and harmonization of technical
separate the manufacturing of such standards and procedures regarding the inspection of
drugs as quinolone, psychotropic, the manufacture of medicinal products and the
penicillin and cephalosporin, etc. testing of medicinal products by official control
Whereas these actions are likely to laboratories, to continue common efforts for the
improve the safety of drugs, unless development, harmonization and maintenance of
accompanied by a true motivation for Good Manufacturing Practice (GMP), and to extend
the industry to comply with the intent the cooperation to other competent authorities having
of these actions, these are likely to the national arrangements necessary to apply
have minimal effect. Ongoing equivalent standards and procedures with a view to
assurance of segregation of drugs contributing to global harmonization.”. Of the
requires a much larger investment European transitional countries, the Czech Republic,
and effort than the creation of a Hungary, Romania, the Slovak Republic and Latvia
facility that appears to comply. In have joined. Only Singapore and Malaysia represent
addition, there are scores of steps that the developing countries. Pakistan is not a member
can seriously compromise the safety of this organization.
of drugs and these include the quality Additionally, the DRA will reach out to all
of starting active raw material, source established agencies including the US FDA for
and quality of inactive ingredients, collaboration on training and qualification of
ability to accurately test the products inspectors, cGMP issues and compliance systems.
and presence of control systems that
17
avoid inadvertent mixing of products. The quality of raw materials (active and inactive)
All of these elements are defined in will be enforced through a system of incentives;
the most rudimentary guidelines there are two types of suppliers: producing GMP and
issued by the WHO for the non-GMP materials. Manufacturers who would use
developing countries. suppliers that have received GMP certification will
be allowed to call their products GMP-Grade. This
allowance by the MOH along with a set of incentives
will foster competition among the manufacturers to
assure compliance. The DRA shall post a list of
manufacturers who use GMP-grade materials to
boost the image of these companies.
Efficacy of drugs can only be assured Until such time that bioequivalence testing
if the final product passes certain tests laboratories are established in Pakistan (one is
of quality. Besides meeting specified underway at HEJ) and until such time that the DRA
physical and chemical tests, the most is able to enforce collection of these data on actual
important test is the demonstration of manufacturing batches, the requirement for
bioequivalence which is now a bioequivalence testing will be waived. Instead, it will
required test for all registration be replaced with the requirement of proving
processes worldwide. Whereas the equivalent dissolution with innovator product; this is
MOH has begun to require this one test that can be done on an ongoing basis and
testing, it is ironic there are no would be made a part of release requirement of each
laboratories in Pakistan qualified to batch. This is a major decision which is presented
do this testing in Pakistan; here as a practical solution. Even if the companies
nevertheless, reports continue to be are able to provide qualified bioequivalence studies,
filed. The entire issue of this is no guarantee that the company will continue
bioequivalence is also misunderstood. to manufacture the same quality product as it used
The bioequivalence studies are for the bioequivalence testing; in many instances
ONLY conducted on an actual companies are known to reference products labeling
commercial batch produced by the as its their product to assure the studies will not fail.
company. In an environment where A more rigorous practical test therefore must be
drug companies first secure something that can be done routinely on each batch.
registration and then begin All companies will be required to produce complete
manufacturing, this is a moot point to stability profile of their products and this should be a
discuss. The same argument applies subject of ongoing audit; however, a certification
to another aspect of efficacy, the from the company under penalty of perjury
stability of drugs; no regulatory declaration the data will be accepted until an audit is
agency in the world allows performed. It is important to hold the heads of
registration unless the manufacturer company responsible for data submission;
demonstrates at least on a three- worldwide, this requirement had significantly
month accelerated study attesting that reduced falsification of data submission to regulatory
the product is stable in its commercial authorities. Falsification of data submitted under the
production batches. Compliance to signature of a CEO would implicate him or her into
both of these basic requirements is criminal punishment. This is a major departure on
almost nonexistent in Pakistan. This how DRA will conduct its operations; the onus of
is further compounded by the responsibility to prove safety of drugs will be shifted
inadequate and unqualified testing of to companies manufacturing drugs and not on the
drugs by the industry. Many review of evidence provided to DRA. Certification
companies do not even have the under penalty of perjury by the CEO of company is
required instrumentation to test, let the only way to enforce compliance. Truthfulness in
alone use the required validated test declaration will be further strengthened through a
methods required by the compendia. peer review process wherein other companies or
These issues multiply when even employees of the company making claims will
18
biological products are in question. have the opportunity to refute. Given these
exposures, it is anticipated that over time, an
environment of truth in declaration will prevail.
To ascertain that the application filed meets the
requirements, the DRA shall adopt the policy of pre-
approval inspection after a report from a third party
regarding the validity of data has been received. To
facilitate this, DRA shall recognized Rapporteurs as
used in Europe to certify validity of data. A company
shall be required to undergo pre-approval inspections
(PAI) once every three years or sooner if a new class
of drugs is submitted. For example, if the DRA has
approved tablet dosage form production by a
company, all other applications in the same dosage
form will not require PAI until the routine cycle of
inspection. If the company files a new dosage form
such as injectable, the company must be inspected
first. A Rapporteur system widely used in Europe is
an example of how the agencies have shortened the
approval times; at the time of submitting application,
the applicant will identify a Rapporteur from the list
of approved Rapporteurs, who will examine the
dossier and confirm the findings through direct
inspection of the facility. This inspection is in
addition to the PAI which is DRA responsibility. The
names of approved Rapporteurs and the files they
have examined and approved will be made available
to the public to allow anyone to submit comments in
case of any perceived irregularity. An office within
DRA shall work on a full time basis examining such
allegations.
Traditional medicines are called part Fortunately, the concerns expressed here have been
of Complementary and Alternative shared by many regulatory agencies worldwide and
Medicine or CAM system and even the US has issued guidelines for botanical
constitute a significant component of products. The purpose of this control will first be to
healthcare in South Asia. Whereas assure safety of drugs and then over years require
much as been said and even some has efficacy assessments as well. The guidelines to
been done to take traditional control herbal or botanical drugs can be either from
medicines under the control of MOH, EMEA such as: 1. „Guideline on quality of herbal
this has not materialized because of medicinal products/traditional herbal medicinal
multitude of factors, mostly political products‟ (CPMP/QWP/2819/00 Rev.1,
but also scientific such as the means EMEA/CVMP/814/00 Rev.1). 2. „Compilation of
of definitive testing of these products. general quality questions addressed by the HMPWP‟
When the health of majority of (EMEA/HMPWP/18123/00 Rev.5). 3. „Guideline on
Pakistanis is at stake, it is specifications: test procedures and acceptance
unconscionable not to take herbal criteria for herbal substances, herbal preparations
drugs into full control; whereas it will and herbal medicinal products/ traditional herbal
be a long evolution process, medicinal products‟ (CPMP/QWP/2820/00 Rev.1,
nevertheless, a beginning should start. EMEA/CVMP/815/00 Rev.1), or the most widely
Homeopathic practice is another area used guideline by the WHO (WHO's Guidelines for
that requires a clear policy making by the Assessment of Herbal Medicines (1991). The
DRA shall adopt at three-phase policy in controlling
19
the MOH. herbal drugs. In the first phase, DRA will issue
registration number to all products without the need
to file any details beyond the details necessary to
track down manufacturers and suppliers. This phase
can be completely very quickly. Immediately after
the expiry of this phase when all products are
brought under recording, safety assessment filings
will be required in accordance with the WHO
guidelines; the use of these guidelines, which are
readily complied with, would allow DRA to escape
criticism of being demanding. In the final phase,
efficacy testing would be initiated.
Homeopathic and biochemic medicines are another
category of uncontrolled drug use but unlike the
herbal products, the potential for side effects is not as
pronounced, except where spurious drugs (e.g.,
tainted with steroids) are involved. Given the scope
and its magnitude, control of homeopathic medicines
will be a lower priority of DRA even though in the
Act, DRA will claim authority to regulate these
drugs as well.
Affordability and Pricing of drugs The most effective price control is competition.
in Pakistan is a long debated topic. However, to avert exploitation and monopolization,
Price control is a politically sensitive the registered in Pakistan will be classified into four
issue; unfortunately, so much has overlapping categories to make drugs more
been written and lot more said about affordable.
this issue that any attempt to appease First, in advice with the WHO, DRA will adopt the
its advocates, one way or other, is no list of WHO Essential Drugs, whose price will be
longer possible. What needs to be strictly controlled. To avert criticism, this list shall
understood is that the goal should be be adopted as given by WHO and would provide
affordability of safe and efficacious affordable therapeutic options for about 90% of all
products, not just pharmaceutical care needed in the country, avoid wasteful and
products. These issues have also
irrational prescribing.
brought in question the credibility of
MOH as frequently the companies are Second category will be the Non-Essential Drugs, all
able to prove inconsistent practices. those molecules that do not fall under the WHO
The current system of pricing is too Essential Drugs List. A price control mechanism for
complex, leaves a lot to discretionary these drugs will be based on competition wherein a
mechanisms and is clearly the cause substantial price reduction will be required upon
of questioned ethical practices. expiry of patents on new molecular entity. It is unfair
to allow different prices to the same product to
different manufacturers; an approval from DRA
constitutes assurance to consumer that the products
are safe and effective; they should then be equally
affordable. However, to foster safety aspects,
companies who are WHO certified and using GMP
grade raw materials and inactive materials will be
allowed a premium and allowed yearly price
increases based on core inflationary rate. It is the
intent to eliminate drugs not manufactured under
environment that assures absolute safety and highest
quality of drugs. To assure that a large number of
20
competitors enter the market simultaneously,
incentives will be given to early filers. It is extremely
important to realize that part of the blame for higher
cost of treatment comes from irrational prescribing
habits compounded by aggressive promotional
practices. Whereas Third category is that of new
molecules, for which a simple formula of
certification (revised every year) that the price
offered in Pakistanis (MRP to MRP comparison
only) the lowest will be required under penalty of
perjury by the CEO of the company selling the
product in Pakistan. The onus of this certification
shifts to the seller and not the MOH. Through a
system of transparency (see below) this will
constitute a self-policing system. Holders of
marketing license of new entities will submit on 10th
July (or the next working day thereof) a revision of
pricing letter indicating that the price charged in
Pakistan is equal to or lower than comparable
marketing areas around the world; for the purpose of
comparison, registered prices on a per unit dose
(where pack sizes are different) as well as
certification of continued approvability in the
country of origin. Should the company fail to file this
certification, the product shall become deregistered
without further notification to the manufacturer.
Appropriate provisions are made in the filing system
to assure that the information provided by the
company is acknowledged. The new WTO
guidelines allow countries like Pakistan to enforce
compulsory licensing of those new molecules that
form the basis of essential lifesaving, for example
the drugs used for the treatment of AIDS. A distinct
division within DRA will study these situations and
make recommendations on such adoptions. This
policy for new molecules will assure that these
products are sold at the lowest price in Pakistan and
where necessary at most affordable prices. DRA will
recognize all intellectual property rights applicable in
Pakistan and will include a substantial expertise in
the area to advise the decision makers, both with
DRA and without.
Fifth category of drugs will be those drugs that do
not require a prescription—the OTC category (it is
important to know that being OTC does not mean a
drug is safe or its price uncontrolled). This
classification is a regulatory exercise and does not
intend to either optimize the price of drugs or their
availability. Manufacturers of OTC class of drugs
will be subject to exactly the same requirement of
cGMP compliance as manufacturers making non-
OTC products. To assure safety of OTC drugs, there
21
shall be two classes of these drugs. One class that
complies with the current US FDA Monograph
requirement. A certification by the company that the
composition, both active and inactive comply with a
current US FDA monograph shall be exempt from
full review process though filing and submission of
registration and renewal fees will be applicable; all
other applications including non-monograph
ingredients will be required to make full and
complete filing and subject to discretion by DRA
whether to allow an OTC status or not. The DRA
may decide to limit filing of the second type of OTC
filing if appropriate safe formulations are otherwise
available in the US FDA monograph.
Sixth category is that of drugs which are best taken
out of drugs category registration such as food
supplements, vitamins and other such products.
Unnecessarily classifying non-drugs as drugs allows
drug companies to promote them through
professional means resulting in greater incidence of
irrational prescribing, additional cost to consumers
and sheer waste of foreign exchange. The decision
regarding this classification will be made on how
identical products are handled in regulated markets.
This segment of classification will also be included
in the public relations campaigns of DRA.
Intellectual Property issues pertain It is important to realize that the MOH can be only
to registration of molecules that are responsible for intellectual property so registered in
still under patent. The WTO and Pakistan. All drug registration applications will
TRIPS mandates have brought great require a proof from the first filer that there are no
responsibility on the MOH and in the Pakistani patents (or foreign patents registered in
List 301 of the US Trade Pakistan) that are infringed; the onus will lie on the
Representative Office this is cited as filer and through the transparency systems
a major violation. The MOH has not introduced, this will be policed by the industry and
defended itself on logistics ground, not the MOH. The issues related to TRIPS will be
which is now a part of the solution decided upon on individual basis and DRA shall
proposed here. have qualified in-house staff to perform this
function.
Distribution of drugs through a Pharmacists play a very important role in healthcare
validated drug supply chain is system by assuring the drugs are used properly and
essential in assuring safety and only upon prescription, pointing out to drug
efficacy of drugs as many drugs interaction possibilities and even in some instances
undergo degradation. Another issue advising patients on the choice of drugs for common
pertains to illegal dispensing of ailments. Several states in the US have prepared a
prescription drugs. This is a thorny separate formulary that the pharmacists can use to
issue. With over 6,000 wholesalers prescribe drugs. DRA shall promulgate rules to
and 60,000 retail outlets dispending streamline the practice of dispensing pharmacies; the
medications almost always without aim will be to mandate record keeping of
the requirement of a prescription (and prescriptions, first for only those drugs which have a
even when so presented, without potential for drug interaction, abuse and overuse.
making any record or history), the Gradually, over years when the infrastructure is
22
health of the Pakistani patients is at available, this should be required for all drugs; this
very high risk. There is a dearth of will also require DRA producing a list of drugs that
enforcement of pharmacy dispensing can be dispensed without prescription (the OTC
rules in Pakistan and it is not likely to category). DRA will create a structure wherein a fee
change in short-term. The variety and could be added for dispensing to allow pharmacies to
size of pharmaceutical activities in a employ pharmacists; currently, most pharmacies
country determine the type and would have a listed pharmacist who would rarely
burden responsibility that the DRA work there as they can not afford to employ
must bear. The larger number of pharmacists. [Incidentally, the number of pharmacist
licensed manufacturers, around 400, reported working in pharmacist is about ten times
with around 30,000 registered higher than the number of pharmacists that exist in
products and broad import of finished Pakistan]. The currently available vigilance force is
products and raw materials, the task insufficient and DRA shall expand its inspection
of DRA can be highly complex to force considerably. Different types of pharmacy
ensuring the quality, safety and licenses will be approved based on the nature of
efficacy of pharmaceuticals. drugs dispensed.
Drug Testing is a vital function of There is a dire need to upgrade the testing
drug control to identify substandard, laboratories operated by the MOH; a new effort to
spurious or counterfeit products. The certify these laboratories by certification authorities
MOH, through its laboratory in ISB will be made. The DRA shall establish a Quality
and KHI conducts the testing of Assurance division to conduct routine audits of these
samples of drugs picked up by the laboratories and provide training to its personnel.
inspectors or those brought in to test [Note: The Quality Assurance Division of DRA shall
for spurious or misbranded drugs. be a supervisory body that would write SOPs for the
entire operations of DRA including its quality
controls aspects; the purpose of QA operations is to
assure that quality is maintained while QC inspects
the quality]. In addition, the DRA will welcome
approved private laboratories at educational
institutions or in commercial setting that are fully
certified to perform this function on an outsourcing
basis.
The weaknesses in the current system of sample
collection will be addressed by creating a system of
accountability of sample collector, evidence creation
and proper storage of samples collected, all in
accordance with standards of crime evidence
creation. Because of the criminal investigation that
can accrue from these studies, extreme care would be
exercises in assuring that the evidence is admissible
in the courts.
DRA shall assure certification of its laboratories to
qualify as reference testing laboratories and also
enforce these standards for provisional testing
laboratories that will be subject to audit by DRA.
DRA shall also establish Appellate laboratories
within its laboratory system or outsource it to other
government or private agencies.
Transparency is a serious issue in In following the lead of other regulatory agencies, all
the developing countries and a cause actions of DRA shall be transparent to stakeholders.
23
of great embarrassment as agencies It will be accomplished through information
like Transparency International provided at the website of DRA and other such
continue to list countries for measures that will assure that discretionary actions
corruption. The long-term success of are limited to minimum and only when warranted. In
DRA will depend on how well it the long run, all discretionary actions will be
gains confidence of all those who are transposed into regulations that will obviate need for
affected by it and this can only be these actions in the future. The purpose of DRA is to
achieved through a perfectly protect health of public and everyone should have
transparent system. The need to be the right to see how various situations are resolved
transparent is widely insisted for the by DRA.
drug control authority for several
reasons that need not be part of this
report. Such claims are widespread
worldwide; the US FDA was plagued
with the problem and then adopted a
system of transparency that is based
on the right of citizens to know the
governance mechanism and as a
result all functional elements are
posted on the website of FDA except
the trade secrets.
Budget. The DRA will be financially To stay self-sufficient, DRA must resort to a policy
self-sufficient organization managed of extremely lean management. As a result, the most
by professional staff. With expected precious component of DRA shall be the headcount
revenue based on the present fee allocated to various functions. Special cuts will be
structure, DRA will have made periodically in the management structure of
approximately Rs. 100 million per DRA to keep it as lean as possible so that it can
year to operate. expand its field resources which are much in need of
expansion. DRA will periodically review its fee
structure to assure that at all times no funds are
needed from the government to operate.
Governance. Drug regulation is a The DRA will be the model paper-less office system
technical function that is often that would rely on least number of headcounts. As a
relegated to non-technical personnel technical agency, DRA will be managed by only
for convenience. The current systems those educationally and professionally qualified to
have evolved over decades and perform these functions. Minimum qualification for
constitute a complex maze of systems any technical entry level will be a degree in
that have overgrown and outgrown pharmacy, medicine or a higher degree such as MS
their utility. or PhD in related fields like pharmacology,
pharmacognosy, medicinal chemistry, physiology,
toxicology, etc.
Documentation forms an essential The DRA will start as a paper-less agency. Every
component of drug regulation, both drug company capable of manufacturing products or
from implementation as well as selling products should be able to comply with
prosecution purposes. The regulatory standardized format for electronic submission and
submissions comprise the largest communication of DRA. Clear guidelines established
paper collection at the MOH by other agencies on the format of submission will
currently and one can see corridors of be replicated instead of creating any new system.
the buildings housing drug control to This will resolve forever the problem of storage, the
be overflowing with document files. physical space requirement and maintaining data
Concerned with the need to maintain security. All submissions will be made in a PDF
24
record as well as reduce the load of format with its embedded security using Acrobat 7.0
receiving, acting, managing and that allows annotation and using the electronic files
archiving documents has resulted in as if they were paper files. For the first time in the
the need for many agencies history of Pakistan, a government agency will work
worldwide to adopt alternate methods without the file folders. Transmission of files within
of handling documentation. the agency will be electronic and all note taking and
comments will be done on screen rather than on
paper. To make sure that those who are not fully
indoctrinated, the comments could be made in
handwriting. This method allows highly confidential
matters to be stored without any security concerns.
The keycodes only need to be secured for the
purpose. DRA will also initiate its policy of
electronic communication using encrypted mail
systems. An advantage of this system is that this will
remove any need for a physical filing system, allow
all correspondence, DRA actions and other
documents to be instantly available for inspection.
This is necessary for DRA to implement its
transparency systems.
Registration Dossiers are currently The evaluation of new drug applications will be
submitted in accordance with a divided into two parts; the evaluation of CMC
specific application format. The section (Chemistry, Manufacturing and Control) and
requirements need to be revised in pharmacology (clinical efficacy and safety); a major
light of the newer requirements of strategic decision needs to be made regarding the
transparency, pricing control, quality level of evaluation that must be established. In
certification, etc as described almost all instances the registration applications
elsewhere in this report. submitted to DRA will be for drugs that have already
been registered in other regulated countries; it is
recommended that the DRA simplify the approval
process for drugs that are established safe and
effective. This is a standard policy for many
developing and even developed countries. A simple
argument offered here pertains to riding the coattails
of others who invest billions of dollars to assure
safety of drug molecules. As a result, DRA will
accept applications for molecules that have already
been approved and come with a proof of free sale in
at least one regulated market. Drug product
registration applications will be received in the
Dockets Division of DRA that will be staffed by
qualified pharmacists, computer personnel as all files
will be received in an electronic form; this two-
member team will then, according to specific SOP,
divide the file into three parts and forward it to the
three DDs. An acknowledgement will be sent to
petitioner within 24 hours of receipt of files that
must be accommodate on a single media (a DVD);
before forwarding the portions cut on special media
to each section, the Dockets Division will assure that
the file meets the format and content layout
requirements. If there are any deficiencies, the
25
petitioner shall be so informed within 7 days of
receipt of files. The system of Rapporteurs (at no
cost to DRA) will allow expediency as it would be in
the interest of companies to provide this reporting.
Each of the sections will prepare its reports and
forward to other sections for review; the first phase
internal meeting will be held among the Directors
and in the event of rejection of application, the
summary reports will be forwarded to Chairman‟s
office for a review. No face to face meeting will be
allowed between DRA staff and any company,
association, client agency, media or any other
individual without prior written permission of the
Chairperson and only when there is an established
need; all meetings and correspondence and telephone
conversation shall be logged in and recorded. The
electronic forms generated and available for
download from the website will be sufficient to make
any possible inquiry; all correspondence, unless it is
confidential for technical reasons shall be posted on
the website through the Dockets Division.
When a company (likely a multinational company)
requests for registration of a new drug in Pakistan,
the company shall submit a certificate stating that the
requested price is the lowest offered by the parent
company in the world. The company will certify on
an yearly basis that the new molecules has not been
recalled from the market, the indications and side
effects reported have not changed and the price of
drug product remains the lowest in Pakistan. All
certificates provided by the company shall be posted
on DRA website for others to refute.
When a company requests registration of a generic
version of a molecule, the company shall provide a
written guarantee that there are no patent violations
through examination of patents filed in Pakistan
only. The assurance given will be posted on the DRA
website and a copy sent to the innovator company to
respond to within 10 days of receipt of intimation. It
is noteworthy that only patents issued in Pakistan are
applicable to Pakistani markets as Pakistan not a
member of any consortium.
Companies wishing to have their product listed as
GMP-Grade will provide certification related to their
WHO audits and use of certified vendors.
Irrational Prescribing of drugs is a Label copy (the insert) should be exactly as it is used
serious health issue as the companies in the country of origin. This is a requirement of the
are currently allowed to create their US FDA and EMEA for generic drugs and so it shall
own label copy (leaflet insert) and be the policy of DRA. Changes even to the font size
what they claim to physicians. It is will not be allowed. Once this has been established it
26
difficult and at times impossible to will be relatively easy for the DRA to control
professionally evaluate the claims promotional media. Through an open system of
made. As a result, the prescribing competitor submission, DRA will welcome receiving
habits have evolved into a quagmire complaints wherein misrepresentations are made;
in Pakistan. where such representations are made, the DRA will
post such violations on its website to warn
physicians. Over time, companies will become more
responsible not for any punitive measure but for
competitive advantage and image of company.
Basic Manufacturing of drugs in It is important to assure that the basic manufacturing
Pakistan is an issue of economic industry provides high class safe product and not a
growth for the country. Whereas product to benefit from any incentives offered by the
specific business development does MOH. It is crucial that the raw material
not fall under the purview of DRA, manufacturing comply with the GMP of basic
economic stimulus to growth of the materials. Similar to the approval of companies as
nation is a job of every agency in the Class A, the raw material manufacturers shall be
country. DRA shall promote required to secure a certification for GMP
development of basic industry in the compliance; such certifications are readily available
country; basic manufacturing has and even simpler to obtain than the GMP
suffered greatly because of lack of certification of a finishing facility. Where there is a
incentives offered for establishment GMP-Grade raw material manufacturer is qualified,
of basic manufacturing and for lack this raw material would then be required to be used
of firm intellectual property laws in by the local industry, unless it is unable to meet the
Pakistan. A comprehensive plan of demand of the industry or is not price competitive
incentives to support basic with a product of similar quality. A certain duty will
manufacturing of quality products be levied on the choice to import raw materials from
will be developed by DRA. However, other countries where a GMP-grade raw material
it must be well understood that it may source is available within the country. This must be
no longer be necessary and in some viewed in light of the WTO provisions as well to
instances no longer possible to assure that the country is not in any violation of the
manufacture a good quality raw treaty. Other incentives that the MOH can offer
material domestically at a cost which without violating any treaty is the preferred
is competitive. The aim will be to registration of product made from locally procured
optimize the need for local raw material.
production with the cost of quality
product.
Structure of the proposed DRA shall DRA shall be a body corporate with its head office at
be formed in line with how other ISB. The agency will be headed by a Chairperson
worldwide agencies work; these appointed by the Federal Government. The
structures have evolved over decades composition of Board will include four Vice
to perform the functions with Chairpersons; the Board may appoint technical
expediency, transparency and committees to be present at the Board meetings. The
accountability. VCs represent the four top-level functions of DRA:
Registration, Compliance, Administration and
Strategic Planning. Under each VC shall be a
number of Directors, who will direct the functioning
of a coherent entity; a coherent entity performs a
complete function leading to a listed objective.
Given below are the twenty functional entities:
Drug Registration
27
Biologics Registration
CAM Registration
Classification and Pricing
Intellectual Property
Dockets
Finance
Legal
Human Resource
General Administration
MIS/IT
Quality Assurance
International Relations
Public Relations
Publications
Research
CE and Training
Inspection
Quality Control
Pharmacovigilence
Each of the entity will then have a structure based on
sub-classification of function. The manpower need
will be justified on the basis of scope of work.
28
Personnel issue is a serious matter The manpower analysis shall be made on a zero-
when it comes to delivering the stated based platform justifying the need for these staff
objectives. Since the DRA proposes a without any consideration of the present structure;
new system of management, the the intent is not to realign the present structure into
manpower will be identified for the DRA but to create a fully justified manpower
defined functions rather than fitting requirement. The headcounts in DRA shall be
the employees to slots. maintained to a minimum level with outsourcing of
whatever function that can be outsourced without
jeopardizing the authority of DRA or safety of health
of Pakistanis. An electronic system of reporting, a
paper-less concept of work and instant connectivity
will guide the structure of the new DRA; individuals
who are qualified to adopt this system will be
inducted and a high level of emphasis will be placed
on the productivity of individuals. In all instance the
DRA shall be a self-sufficient authority requiring no
funding from the Government of Pakistan from the
very beginning and managed like a commercial
corporation with full accountability of all of its
functions by the management. As a corporate body
the agency will have full rights to remove anyone
from employment without consequences and with
expediency afforded to private businesses.
Redundancy of tasks is a serious The DRA will encourage establishment of a
problem in the globalization of pharmacopoeia for CAM products where such
regulatory matters; for decades, the specifications are not available in the world. The
major regulatory authorities have purpose of this exercise will be to assist
been working on consolidating manufacturers of CAM products to standardize their
policies, regulations and compliance products. It is noteworthy from a legal perspective
documents. The International that the regulatory agencies not adopt any
Conference on Harmonization is a pharmacopoeia as binding standards; even in US, the
clear example of this recognition. FDA recommends using USP specifications but the
Whereas nationalistic dictum might FDA is not bound by these recommendations and
encourage creation of indigenous can enforce different standards where necessary.
systems, the cost of creating A close collaboration with the WHO on
regulatory systems and keeping them documentation will reduce the work load
current are clearly prohibitive, considerably; keep the documents current and
redundant and wasteful. Examples policies defendable.
include suggestions to establish a
Pakistan Pharmacopoeia. Even in the
US, the function of creation of
pharmacopoeia is outsourced to a
private agency since the cost of
creating standards is prohibitive.
However, there are instances where
indigenous standards need to be
established when they are not
available elsewhere. When it comes
to regulatory policies such as cGMP,
bioequivalence, etc., it is clearly
indicated that the agencies should
adopt existing policies, particularly
29
since the WHO has gone to great
length and expense to create these for
the developing countries.
30
Proposed Regulatory System
Legal Status:
The proposed Drug Regulatory Authority has been recommended by the WHO‟s Technical
Advisory Group, and duly endorsed by the Ministry of Health, as to be a xxx body which is
“technically, administratively and financially autonomous working under the Ministry of Health.”
Vision Statement:
To be the most effective, transparent and respected drug control authority.
Mission Statement:
1. To assure that drugs available in Pakistan are safe and effective.
2. To assure that the drugs available in Pakistan are offered at the most affordable prices compared
to other countries with similar affordability.
3. To promote rational use of drugs in Pakistan
4. To implement the eGovernance model of management
5. To deliver services on most efficient, prompt basis to the citizens of Pakistan: Health for All
6. To promote indigenous production of quality raw materials and promote export of drugs as a
source of foreign exchange revenue for Pakistan.
Objectives:
1. To ensure organization efficiency and effectiveness through modernization and automation of
office, laboratory licensing, registration and surveillance system and regular review and
improvement of services.
2. The strengthen enforcement activity of the related legislation through substantial expansion of
the investigative staff.
3. To create a totally transparent system of governance which evolves continuously based on
customer needs.
4. To enhance professional skills of the staff through an aggressive continuing education program.
5. To offer a continuing education program for the industry on the issues of cGMP and
compliance.
6. To secure liaison and networking with global regulatory authorities to secure assistance in
helping achieve the missions of the agency.
7. To promote public health by ensuring the quality, safety and efficacy of all types of drugs, as
defined in the Drug Act, sold in Pakistan.
8. To develop and promote the concept of essential drugs and to ensure regular, uninterrupted and
adequate availability of such drugs of acceptable quality and at reasonable price;
9. To create a system of monitoring and education that will promote rational use of drugs ,
31
particularly to safeguard the public from overuse, abuse, or misuse of drugs.
10. To encourage basic manufacturing of quality raw materials and export of finished products
from Pakistan.
11. To vigilantly confront the problems of spurious and counterfeit drugs.
12. To train manpower to perform the functions entrusted with a view of modernization of the
methods of investigation, surveillance and prosecution.
13. To promote research to resolve contemporary challenges in delivering the mission of the
agency.
14. To strengthen and monitor pharmacy services including distribution chain, dispensing practices,
patient profiling, etc.
15. To ensure supervision of distribution chain.
Powers:
The DRA shall be exclusively responsible for the registration/enforcement/regulation of the
provisions of Drugs Act, 1976 and the xxx thereof from time to time. In performing its functions
under this Act, the Authority shall, as far as practicable protect the interests of consumers and
pharmaceuticals in accordance with guidelines, not inconsistent with the provisions of the Drugs
Act, 1976 laid down by the Federal Government. An organogram for the proposed DRA is
provided. In particular, and without prejudice to the generality of the foregoing only the authority,
subject to the provisions applicable shall:
1. Registration of drugs as defined in the Drug Act
2. Regulate import and export of drugs.
3. Regulate manufacturing of drugs.
4. Regulate pricing of registered drugs.
5. Regulate of advertisements and promotional activities.
6. Establish and regulate Federal Drug Testing Laboratories and create and implement laboratory
standards for provincial testing laboratories.
7. Monitor the quality, safety and efficacy of drugs.
8. Regulate clinical trials of new and existing drugs.
9. Promote research to resolve contemporary problems.
10. Promote bulk manufacturing where necessary and practical.
11. Prescribe fees for various services rendered by the Authority.
12. Establish liaison with international agencies for obtaining assistance for strengthening of the
activities, which is incidental or consequential to any of the aforesaid functions.
Human Resource Requirements:
The manpower required to perform the functions envisioned is derived from specific activity (the
functional units described above). On a higher level, the main function of DRA is to register
products and to assure they continue to comply with safety, efficacy and affordability requirements.
These two broad functions are supported by administrative support function and a strategic policy
section. Under the four major divisions will be distributed the twenty functional entities that,
together, provide coverage to all objectives of DRA.
32
It is realized that every function of DRA is of technical nature and as a result, the human resource
development in technical areas is of extreme importance. It is further realized that the human
resource required to perform these functions is highly expensive. Efforts will be made to secure
highly accomplished and qualified individuals at market-competitive salary and benefits packages.
It is inevitable therefore for DRA to have a two-track system of employees: one for those who are
part of the Civil Services system and the other those of privately employed by DRA. Individuals
may be hired on a contract basis, to fill in short-term requirements. An elaborate training program
and CE program will supplement development of qualification of DRA employees. It is anticipated
that whereas the cost manpower will be higher, this will be partly compensated by higher
productivity; this is reflected in the smaller number of headcounts requested.
In general, the minimal qualification to enter DRA shall be a bachelor‟s degree, except for the
maintenance staff where the minimal requirement shall be high school. The minimum qualification
for administrative support staff shall be MA in English or professional pharmacy degree with
excellent command of English language and communication skills. The plan presented below
require a total manpower requirement of about 323 people, less than the current number employed
by the Drug Control Organization of the Ministry of Health. Given below is a de tailed description
of the twenty functional units and four top level secretariats and their human resource requirements:
The HRD of DRA shall establish a comprehensive human resource development policy for career
development, promotions and continuous evaluation of employee performance; a structured system
based on MBO shall be initiated wherein on an yearly basis, all employees will be informed of their
evaluation that will clearly identify their strengths and weaknesses and plans to rectify the
weaknesses within fixed timetable.
Chairperson Secretariat will be responsible for the management of all functions of DRA,
coordination of inquiries from legislative bodies, create long term vision, create budgeting
resources and provide an ongoing evaluation of DRA. The directorate will issue annual reports on
its functions, accomplishments, achievement of goals and other related subjects. Also, all inquiries
for reporting from the Cabinet or other legislative bodies shall be attended by this office.
Chairperson, DRA will hold a PhD in pharmaceutical sciences from a reputable foreign university,
have over ten years of experience in pharmaceutical regulatory environment, excellent
communication and networking skills, and visionary leadership are required. Total staffing: 5: PhD
(1), MA (2), MBA (1), Pharmacist (1)
Vice Chairperson Secretariat Strategic Planning Division will be responsible for establishing
SOPS for the authority and enforce their compliance, analyze research needs and fund projects to
resolve issues of importance to DRA, establish international liaison with regulatory and funding
authorities to support DRA, create and deliver an aggressive CE and training program for
employees of Authority as well as educate the pharmaceutical industry about cGMP compliance.
The SPD shall create and revise vision and mission statement, issue annual reports on
accomplishments, and develop an intensive public relations campaign to further the goals of
Authority, particularly with reference to awareness about safety and efficacy of drugs, proper
prescribing practices and drug abuse potential. The VC shall be a prominent scientist in the
pharmaceutical or medical field with advanced training in drug regulatory management. Total
staffing 5: (PhD (1), MA (2), Pharmacist (1), MBA (1).
CE/Training Directorate shall have the responsibility of training both the DRA staff and
to impart CE training to the industry, pharmacy chains and any other health professional
who is involved in handling drugs. This is a newer function of DRA and based on the
recognized need that the safety and efficacy of drugs can not be assured just by punitive
measures. It is important that all those who are involved in delivering services and those
involved in monitoring them understand fully the need for regulation, the extent and scope
of the legal issues and consequence of non-compliance. All employees of DRA will be
required to complete some type of CE every year as part of their annual review. DRA shall
offer a large number of training programs, both on campus and off campus. Most important
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in imparting cGMP training to the industry will be the impression that the purpose of the
training staff is to assist. The Director shall hold a doctorate in education from a foreign
university with at least 10 years of teaching experience particularly in imparting
professional education. Excellent communication skills, leadership talent and ability to
network with the industry, the professional groups is required. Total staffing 14: EdD (2),
PhD (4), Pharmacist (5), MA (2), MBA (1).
Research Division shall be responsible for the disbursement of the research fund levied by
the MOH; the purpose is to support healthcare systems in Pakistan. Given the fact that many
issues remain unresolved regarding the safety and efficacy testing of drugs, the funds will
be directed to those studies, particularly in developing standards for CAM drugs like
botanicals. The research funds will be disbursed through a RFP (request for proposal)
wherein the Division shall identify the problems and invite scientists around the country to
help resolve these issues. The Director shall hold a PhD degree in pharmaceutical sciences
with extensive publications record in international journals (peer reviewed), have an
impeccable research achievement record, and have excellent communication and leadership
qualities. Total staff 4: PhD (2), Pharmacist (2).
Quality Assurance Directorate will be responsible for writing, keeping updated and
monitoring compliance with an extensive set of Standard Operating Procedures that apply to
the entire DRA; this is a new function of DRA and considered the most important function
to deliver the goals and objective envisioned by DRA including the challenge to be
transparent. DRA shall be an ISO certified facility. The Director shall hold a MBA in
management, be fully conversant with the writing of SOPs and their management through
an electronically driven enforcement and recording system. Total staff 6: MBA (4), MA (2).
International Relations Directorate will be responsible for establishing networking with
worldwide regulatory agencies, will serve as focal point of all communications with the
WHO, arrange exchange programs and secure funding available to support DRA activities
from international sources. The Director shall hold MBA in Management, have worked
worldwide, demonstrate leadership and communication skills. Total staff 3: MBA (1),
Pharmacist (1), MA (1).
Public Relations Directorate will be responsible for publicizing rational prescribing
practices making physicians and public aware of the importance of using essential drugs
only; hold seminars and meeting to promote availability of safe, effective drugs at
affordable prices. All public queries regarding the functioning of DRA will be routed
through this directorate, whose director shall be the spokesperson of DRA. This important
to assure uniform policies are distributed. The Director shall hold an advanced degree in
clinical pharmacy or a physician board certified in internal medicine with demonstrated
record of public relations for at least 10 years, be fluent in English, Urdu and preferably
regional languages; leadership quality and ability to handle press are required. Total staff 3:
PhD or MD (2), MA (1).
Publications Directorate will be responsible for publishing targeted volumes; DRA will
prepare a Herbal Pharmacopoeia and keep it updated; other publications will include a
comprehensive guideline on manufacturing essential drugs, test methods to verify their
safety and efficacy and methods of validating test methods. The directorate will also publish
monographs on OTC drugs to streamline the composition of these products; this is required
to assure safety of those products which will be allowed to be sold widely without
prescription and in some instances without lengthy registration process. This is a new role
of DRA that aims to provide tools, guidance and assistance to manufacturers and users of
drugs correct information about drugs. Periodic publications will include guidance on
disease management and the website of DRA will have a well-defined section that will
answer questions relating to use and abuse of drugs. It is noteworthy that this directorate
will be assisted by all directorates of DRA for technical support. The Director shall hold a
34
PhD in pharmacy, have demonstrated record of writing and publishing skills. Total staff 5:
PhD (2), MA (3).
Vice Chairperson Secretariat Registration will be responsible for the registration of all types of
drugs in Pakistan; this includes chemical drugs, biological drugs, CAMs and any other compounds
used in accordance with the definition of drug in the Drug Act 1976. There will be three distinct
registration divisions of registration, chemical drugs, biological drugs and CAM headed by
Directors; in each Division, there will be further three departments: CMC, pharmacology/clinical,
and medical. These divisions will be supported by Intellectual Property, Classification and Pricing
Divisions; this will be the second largest function of DRA. The Secretariat will be headed by a
prominent scientist with established track record of research as well as hands on experience in
working with major regulatory authorities around the world. Ability to lead a highly talented and
motivated scientific group is required. Total staffing: 3: PhD (1), Pharmacist (1), MA (1)
Chemical Drugs Directorate shall be responsible for registration of small molecule
chemically derived drugs for all types of classifications including local manufacture, import
or export. Conduct of clinical trials where needed or requested shall be approved by the
Medical section of the directorate. The Director shall hold a PhD in pharmaceutical sciences
from a reputable foreign university; have international experience working as a regulatory
person or in a regulatory agency. Excellent communication and management skills are
required. There will be five managers under the director including: Manager CMC Section,
Manager Pharmacology and Clinical, Manager Medical; Managers will hold at least a
professional degree in pharmacy or medicine (for pharmacology, clinical and medical), have
excellent communication and writing skills. Postgraduate training is required. Support staff
shall have at least a pharmacy degree or medical degree. Total staffing: 26: PhD (10),
physician with postgraduate qualification (4), Pharmacist (10), MA (2).
Biological Drugs Directorate shall be responsible for registration of large molecule
biological derived biological products for all types of classifications including local
manufacture, import or export. Conduct of clinical trials where needed or requested shall be
approved by the Medical section of the directorate. The Director shall hold a PhD in
pharmaceutical sciences from a reputable foreign university; have international experience
working as a regulatory person or in a regulatory agency. Excellent communication and
management skills are required. There will be three managers under the director including:
Manager CMC Section, Manager Pharmacology and Clinical, and Manager Medical;
Managers will hold at least a professional degree in pharmacy or medicine (for
pharmacology, clinical and medical), have excellent communication and writing skills.
Postgraduate training is required. Support staff shall have at least a pharmacy degree or
medical degree. Total staffing: 6: PhD (2), MBBS or MD (1), Pharmacist (2), MA (1).
CAM Directorate shall be responsible for registration of complementary and alternative
medicine drugs derived from botanical, mineral, homeopathic, biochemic sources etc., for
all types of classifications including local manufacture, import or export. This is a newer
activity for DRA and whereas initially the staffing needs may be smaller, eventually this
division will be the largest division in DRA since majority of the Pakistani population
benefits from these drugs. Conduct of clinical trials where needed or requested shall be
approved by the Medical section of the division. The Director shall hold a PhD in
pharmaceutical sciences from a reputable foreign university; have international experience
working as a regulatory person or in a regulatory agency. Excellent communication and
management skills are required. There will be three managers under the director including:
Manager CMC Section, Manager Pharmacology and Clinical, and Manager Medical;
Managers will hold at least a professional degree in pharmacy or medicine (for
pharmacology, clinical and medical), have excellent communication and writing skills.
Postgraduate training is required. Support staff shall have at least a pharmacy degree or
medical degree. Total staffing: 11: PhD (2), Tabibs, graduate and licensed (3), Homeopaths,
35
graduate and licensed (2), Pharmacist (2), MA (2).
Medical Device Directorate shall be responsible for development of specification and
approval criteria of medical devices for use by Provincial agencies as defined in the Medical
Devices Act of 2006 (pending approval). The Directorate shall be headed by a pharmacist
with advanced degree or experience in regulatory management of medical devices. Total
Staff 3: Pharmacist (2); MA (1).
Intellectual Property Directorate will assure compliance with the existing laws of the
country particularly those related to WTO‟s TRIPS provisions. The Director shall be a
patent lawyer preferably with a foreign licensing to practice patent laws; full familiarity
with TRIPS issues, a clear thinking on implementation of law and excellent communication
skills are required. Total staffing 2: Patent Lawyer or Agent with foreign license (1), MA
(1).
Classification and Costing Directorate shall be responsible for creating and maintaining
policies for the pricing of drugs in different classifications. This is a newer function for
DRA wherein all drugs registered shall be either classified as essential or non-essential
based on strict guidelines of the WHO; also falling under the purview of this division is
declassification of drugs. Pricing of drugs is a highly sensitive issue which goes beyond
competitive pricing. This is also a highly political issue that requires serious policy making
that can be well defended. Public relations efforts to familiarize the public and the
legislature with the appropriateness of actions of DRA are required. The Director shall hold
a CA qualification. Total staffing 6: CA (1), MBA (1), Pharmacist (2) M.Com or B. Com
(2).
Dockets Directorate shall be responsible for receiving registration applications in a
prescribed electronic form; paper correspondence will be converted to electronic form prior
to forwarding it to appropriate offices; all original receipts shall be filed in a safe vault; only
those paper documents that have a legality to be kept in original signature, all other paper
will be discarded through shredding process. The Directorate will have a specific function
of validating the receipt of material and then distributing it to specific department through
uploading the files and through an automated system, alerting the department to respond.
The Director shall hold a MBA in Management or MIS with track record of managing
correspondence, electronic data management etc. Total staff 8: MBA (3), PhD (2), MA (3)
Vice Chairperson Secretariat Administration shall be responsible for delivery all support
functions for DRA including legal, finance, maintenance, human resource, MIS/IT, legal. The VC
shall hold a MBA degree from a foreign university with 10+ years of top level management
experience in a multinational company in any field. Total staffing 2: MBA (1), MA (1).
Legal Affairs Division shall be responsible for legal matters relating to the legal framework
of DRA, its prosecution activities and all matters that require interpreting laws on behalf of
DRA. The Director shall be an attorney with over 10 years of litigation experience in High
Court or Supreme Court. Total staffing 3: Lawyers (2), MA (1).
Human Resource Division will be responsible for recruitment, training (skills
development, different from the CE offered by the professional training department), and
performance evaluation, management by objective compliance and incentive program
management. The Director shall hold an MBA from a reputable institution with over 10
years experience in managing large professional staff; ability to motivate, communicate and
leadership are required. Total staffing 6: MBA (3), MA (3)
Finance Directorate shall manage the finances of DRA, audit accounts, manage payroll,
establish and update user fee structure and prepare annual reports and incentive and benefits
programs of DRA. Since DRA shall be a financially independent organization, cost control,
head count minimization and waste control are essential to its success. The Director shall
36
hold a CA qualification from a reputable university with over ten years of experience with a
major pharmaceutical company or a MNC. Total staffing 7: CA (3), MBA (2), M. Com (2).
MIS and IT Directorate shall be responsible for data management, creation and
maintenance of extensive web presence, electronic documentation and creation and
maintenance of a paper-less working system. The Director shall hold a engineering degree
in IT and will have 10+ years of experience of managing MIS and IT at a major
commercial, preferably pharmaceutical, company. Total staff 14: BSIT/MSIT (3), MBA (2),
Computer Science graduate hardware (1), Computer science graduate software (3), Web
designers (1), Computer science graduate networking (2), MA (2).
Facilities Management Directorate shall be responsible for the management of physical
facility housing DRA, utilities, services, protocols, visits, security of personnel and data.
The Director shall hold a BE from a reputable university. Total staff 14: BE (1), DAE, one
civil and one electrical (2), HS (10), MA (1)
Vice Chairperson Secretariat Compliance shall be responsible for the implementation of
provisions of DRA actions. This will be the largest unit in DRA that will serve inspection functions
for manufacturing units, distribution channels, pharmacovigilance, and port operations. The VC
shall hold PhD degree in pharmacy and have 10+ years of regulatory compliance experience
working with well-developed regulatory agencies worldwide. Total staffing 3: PhD (1), Pharmacist
(1), MA (1).
Inspections Directorate shall be responsible for conducting inspections of manufacturing
facilities, distribution channels including wholesale and retail outlets and other such
facilities where the drugs may be handled. Inspections include pre-approval inspections,
new facility inspections, routine cGMP compliance inspections and complaint-directed
inspections. This is one of the most neglected areas requiring a large contingent of staff to
monitor about 400 manufacturing facilities, about 6000 wholesalers and over 60000 retail
outlets in addition to hospitals, clinics and other facilities where drugs are handled. The
Director shall hold a PhD degree in pharmaceutical sciences and also a pharmacist with
extensive manufacturing experience and advanced training in cGMP compliance, regulatory
compliance and understanding of law is required. Ability to educate and train staff is also
required. There shall be four offices outside of the central premises from where the
inspectors will work. Total staffing 111: PhD (4), Pharmacist (75), MA (12); HS (20).
Pharmacovigilence Directorate shall have the responsibility of post-market surveillance,
adverse drug reactions, utilization and appropriateness of use of drug and trend analysis in
prescribing habits, establishment and management of a Drug Information Center and Poison
Information Centers, promotional and advertising compliance. This is an additional function
for DRA and aims to determine abuse potential and prescribing habits. The Director shall
hold a pharmacist with clinical qualification from a reputed university and have excellent
familiarity with market survey tools, ability to summarize findings and converting them into
proactive policies is required. Total staffing 10: Clinical Pharmacist (3), Pharmacist (5), MA
(2).
Quality Control Directorate shall be responsible for managing the testing laboratories
managed by DRA in Islamabad, Karachi or wherever they are installed and operated; an
effort will be made to consolidate these laboratories to reduce the overhead cost of keeping
the laboratory certification. All laboratories of DRA shall be certified through party
international certification as reference testing laboratories. DRA also create standards for
certification of provincial drug testing laboratories; perform necessary audits to assure
compliance with the standards of a reference testing laboratories. The results of DRA
laboratories shall be challengeable and resolved through intervention of an Appellate
Laboratory as designed by the DRA. The appellate laboratory can be a separate laboratory
within the DRA or an outside laboratory such as at NIH or in a private institution. The
37
Director shall hold a PhD degree in chemistry with over 15 years of managing QC
laboratories in a multinational pharmaceutical company; complete awareness and leadership
to secure international certification is required. The bench level chemist will have a PhD or
MS degree in analytical chemistry, and microbiology. The Directorate will have its own QA
staff to assure compliance. All laboratories will be ISO certified and third party certified as
reference test laboratories. Total staff 49: PhD (25), MS or M Pharm (10), BS (7), MA (2),
HS (5).
Licensing Directorate will be responsible for approving new facility design and GMP
compliance as well as ongoing assurance with cGMP in plant modifications and compliance
with any new directives of DRA. The Directorate shall be headed by a pharmacist with
extensive experience in cGMP compliance. Total staff 4: Pharmacist (3), MA (1).
Promotional Compliance Directorate will be responsible to assure that the media or other
modalities of advertising by the drug companies.
38
39
Administrative Structure of DRA
Chairman
VC, Strategic Planning VC, Registration VC, Compliance VC, Administration
Director, Research Director, Chemical Drugs Director, Inspections Director, Gen
Administrati
Director, Quality Affairs Director, Biological Drugs Director, Pharmacovigilence Director, Human R
Director, International Director, CAM Director, Quality Control Director, Fina
Relations
Director, Public Relations Director, Classification Director, MIS
and Pricing
Director, CE Director, Intellectual Property Director, Legal
and Training
Director, Publications Director, Dockets
