GDP Annex to ISO 9001 draft 20091222 for review - DOC by 4A83AJ

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									                                          Annex to ISO 9001:2008
                       Additional requirements for GDP for Pharmaceutical Excipients
           based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

 1   0       Introduction
 2           This document is an annex to ISO 9001:2008. Organisations requiring certification to this Annex shall
 3           hold a current ISO 9001 certificate. Assessment against the requirements of this annex and ISO 9001
 4           may be conducted simultaneously.
 5
 6   0.1     General
 7           Excipient distribution shall be carried out in accordance with Good Distribution Practices (GDP) consistent
 8           with this Annex. The objective of excipient GDP is to maintain pharmaceutical excipient quality and
 9           consistency, whilst ensuring traceability of the material throughout the entire supply chain.
10
11           Pharmaceutical excipients are substances other than the Active Pharmaceutical Ingredient (API) that
12           have been appropriately evaluated for safety and intentionally included in a drug delivery system.
13
14           Throughout this document, references to “GDP for pharmaceutical excipients” will be referred to as “GDP”
15           and “excipients” to mean “pharmaceutical excipients”.
16
17           Parties involved in the supply chain shall be aware that an excipient can only be pharmaceutical grade
18           when it is in compliance with pharmacopoeial specification (if existing for the specific excipient) and/or
19           appropriate regulatory requirements and is manufactured, repackaged, and handled in accordance with
20           excipient GMPs (e.g. IPEC-PQG Excipient GMP, WHO Excipient GMP).
21
22           Throughout the document there are parentheses in the form (ref) and [ref], the former referring to sections
23           in this document and the latter to the IPEC Good Distribution Practices (GDP) Guide for Pharmaceutical
24           Excipients.
25
26           Where a list does not start with “a)” then it is an addition to the text of the corresponding paragraph in ISO
27           9001, e.g. in 6.2.2, where the list starts with” f)”.
28
29   0.2     Process approach
30           No additional requirements to ISO 9001.
31
32   0.3     Relationship with ISO 9004
33           No additional requirements to ISO 9001.
34
35   0.4     Compatibility with other management systems
36           No additional requirements to ISO 9001.
37
38   1 Scope
39   1.1 General
40        In this Annex the term “if/as applicable” is used several times. When a requirement is qualified by this
41        phrase, it is deemed to be “applicable” unless the organization has documented a risk assessment which
42        concludes that it is not applicable. This process shall also be followed where operations covered in this
43        Annex are not carried out by the organization (outsourced). The “Matrix of Applicability” included as table
44        1 in the IPEC GDP Guide may be used as guidance to decide applicability.
45
46           Purpose and Scope
47           No additional requirements to ISO 9001.
48
49           The Annex and its Use
50           Note:
51           The Annex should be used in conjunction with the current IPEC Good Distribution Practices Guide for
52           Pharmaceutical Excipients which provides detailed guidance.
53
54   1.2     Application
55           This Annex includes requirements additional to that required for ISO 9001:2008 certification purposes. It
56           is applicable also for e-commerce [1.6].
57
58           This Annex allows organizations to demonstrate conformance with GDP for the:
59                     transportation of bulk or packed excipients
60                     warehousing (storage of packed excipients)


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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
                DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

 61                      brokering, trading, and reselling of packed excipients
 62                      re-packaging and processing
 63                      sampling, testing, and re-testing
 64                      relabeling
 65                      bulk handling and bulk storage
 66
 67   2       Normative references
 68           No additional requirements to ISO 9001.
 69
 70   3       Terms and definitions
 71           See section “Definitions and Glossary”.
 72
 73   4       Quality management system
 74   4.1     General requirements
 75           The organization shall ensure that the principles of GDP are applied where distribution activities, as noted
 76           in 1.2 (e.g. warehousing, transportation, sampling, labelling, packaging, testing) are outsourced.
 77
 78   4.2 Documentation requirements
 79   4.2.1 General
 80         The Quality Management system documentation shall include:
 81         e) the organization’s overall intentions and approach to GDP
 82         f) documented procedures required for compliance with this Annex
 83         g) documented risk assessment that defines when the “as applicable” clauses in this Annex are not
 84         implemented.
 85
 86   4.2.2 Quality Manual
 87         The organization shall establish and maintain a quality manual that includes or references:
 88         d) a definition of the extent to which this Annex applies to its quality management system and its business
 89         processes.
 90
 91   4.2.3 Control of documents
 92         The Quality Unit shall review and approve documents that impact product quality, including changes to
 93         these documents.
 94
 95           The department with the responsibility for issuing documents shall be identified. Documents that impact
 96           product quality shall be reviewed and approved by the Quality Unit.
 97
 98           Note: The Quality unit may delegate this responsibility, unless otherwise noted herein if appropriate
 99           controls are in place and are documented (see 5.5.1).
100
101           If electronic signatures are used on documents they shall be controlled to provide equivalent security to
102           that given by a hand written signature.
103
104           Certificates of Analysis (COAs) are documents that are critical to ensure product traceability. Documented
105           processes shall be implemented to ensure control of COAs. [6.3, 6.4]
106
107   4.2.4 Control of records
108         Entries in quality records shall be clear, indelible and made directly after performing the activity (in the
109         order performed), signed and dated by the person performing the activity and making the entry.
110         Corrections to entries shall be dated and signed, leaving the original entry legible.
111
112           Quality records shall be kept for a defined period. This period shall be appropriate to the excipient and its
113           expiry date or retest interval.
114
115   4.3     Change Control
116           There shall be a documented procedure for the evaluation and approval of changes that may impact upon
117           the quality of the excipient. The evaluation and approval of changes shall occur prior to the
118           implementation of the changes. An independent unit shall approve changes that may impact on the
119           quality of the excipient. Where the impact on the quality of the excipient is significant, changes shall be



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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
                DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

120           communicated in advance whenever possible to customers and, as applicable, regulatory authorities (see
                    1
121           7.2.3) .
122
123           The responsibilities and requirements for evaluating, managing, implementing change and maintaining
124           records (see 4.2.4) shall be described in a documented procedure.
125
126   5.      Management responsibility
127   5.1     Management commitment
128           Top management shall provide evidence of its commitment to GDP by:
129            f) ensuring that GDP objectives are established, and
130            g) communicating to the organization the importance of conforming to GDP.
131
132   5.2     Customer focus
133           Top management shall ensure that customer requirements related to GDP for pharmaceutical excipients
134           are determined and met.
135
136           The organization shall permit audits to review its quality management system, records, excipient handling
137           processes, buildings and facilities.
138
139   5.3     Quality Policy
140           Top management shall ensure that the quality policy:
141            f) includes a commitment to the implementation of GDP.
142
143   5.4 Planning
144   5.4.1 Quality objectives
145         Top management shall set objectives for adherence to GDP.
146
147   5.4.2 Quality Management system planning
148         No additional requirements to ISO 9001.
149
150   5.5 Responsibility, authority and communication
151   5.5.1 Responsibility and authority
152         An independent unit such as the Quality Unit shall be responsible for:
153              ensuring quality critical activities are undertaken as defined,
154              approving suppliers of quality critical materials and services,
155              approving or rejecting packaging components and excipients,
156              authorizing changes to processes, specifications, procedures, test methods and investigating
157                failures and complaints (see 4.3),
158              developing and implementing an internal audit program.
159
160           Levels of authorization shall be clearly defined in formal job descriptions or in contracts [2.2].
161
162   5.5.2 Management representative
163         No additional requirements to ISO 9001.
164
165   5.5.3 Internal communication
166         GDP and regulatory requirements shall be communicated as appropriate throughout the organization.
167
168           There shall be a documented procedure that describes how top management are promptly notified about
169           any quality critical situations (for example those that would lead to a product retrieval from the market).
170
171   5.6   Management review
172   5.6.1 General
173         No additional requirements to ISO 9001.
174
175   5.6.2 Review input
176         No additional requirements to ISO 9001.
177

        1
            IPEC-Americas Significant Change Guide

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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

178   5.6.3 Review output
179         No additional requirements to ISO 9001.
180
181   6      Resource management
182   6.1    Provision of resources
183          The organization shall determine and provide the resources needed:
184           c) to meet the GDP requirements of this Annex.
185
186   6.2 Human resources
187   6.2.1 General
188         Records shall be maintained listing the name, address and qualifications of consultants who provide
189         advice concerning any aspect of this Quality Management System and the type of service they provide.
190
191   6.2.2 Competence, training and awareness
192         Training shall be recorded and the organization shall:
193          f) ensure training includes
194               i. GMP and GDP principles and the contents of this Annex,
195               ii. the risk of contamination to excipient quality,
196               iii. the potential hazard to end user/patient if an excipient is contaminated,
197               iv. the potential impact on customer’s product quality resulting from any departures from specified
198                    procedures,
199               v. the risk of excipient contamination from deficiencies in personal hygiene, and
200               vi. the reporting of significant failures and deviations from procedures
201          g) conduct appropriate initial and refresher training at defined intervals.
202
203   6.2.3 Personnel Hygiene
204         Where excipients are exposed to the environment, the organization shall control personnel hygiene and
205         require appropriate protective apparel to ensure the product is not contaminated. Jewellery and other
206         loose items shall be either removed or fully covered. Only authorized personnel shall enter those areas of
207         the buildings and facilities designated as limited access areas.
208
209          If the excipient is exposed, documented procedures shall be in place for personnel hygiene programs.
210
211          Personnel shown to have an apparent illness or open lesions that may adversely affect the safety or
212          quality of the excipient shall be excluded from direct contact with raw materials, packaging components,
213          intermediates, and finished excipient.
214
215          The storage and use of food, drink, personal medication, tobacco products or similar items shall be
216          restricted to certain designated locations separate from operational warehousing and laboratory areas.
217
218   6.3    Infrastructure
219          Premises and equipment shall be located, designed, constructed, adapted and maintained to suit the
220          operations to be carried out. Their layout and design shall aim to minimize the risk of contamination and
221          errors and permit effective cleaning and maintenance in order to avoid cross-contamination, mix-ups,
222          build-up of dust or dirt and, in general, any adverse effect on the quality of materials [3.1, 5.1].
223
224          Dedicated equipment should be used where possible when handling and/or processing pharmaceutical
225          excipients. Where non-dedicated equipment is used, appropriate cleaning procedures and effective
226          cleaning schedules shall be maintained and recorded.
227
228          The effectiveness of cleaning procedures shall be verified [5.8].
229
230          Where the excipient packaging is opened or the excipient is packaged from bulk:
231            The infrastructure shall be managed, operated, cleaned and maintained in accordance with GDP to
232             avoid contamination (arising from particulate matter, microbiological risks, utilities, and equipment
233             lubricants and coolants that may come into contact with the excipient).
234            Equipment shall be commissioned before use to ensure that it is functioning as intended. The use,
235             cleaning and maintenance of quality critical equipment shall be recorded.
236            Packaging processes carried out where there is a risk of exposure to highly sensitizing or toxic
237             materials (e.g. herbicides or pesticides) shall use dedicated equipment unless appropriate measures


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                                         Annex to ISO 9001:2008
                      Additional requirements for GDP for Pharmaceutical Excipients
          based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
             DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

238            to avoid cross-contamination have been implemented and the effectiveness of these measures has
239            been demonstrated.
240           The possibility of contamination caused by direct operator contact shall be evaluated and controls
241            implemented if the excipient is at risk.
242           Equipment with moving parts shall be assessed with regard to the integrity of seals and packing
243            materials to control the risk of contamination.
244
245        Where computerized systems may impact upon excipient quality there shall be sufficient controls for their
246        operation and maintenance to prevent unauthorized access or changes to computer software, hardware
247        or data. There shall be:
248            Evidence that demonstrates the equipment and software are performing as intended,
249            Retention of suitable back-up or archival systems, and
250            Assurances that changes are verified and documented and made only by authorised personnel.
251
252        Water, where used in contact with excipients shall be demonstrated to be of a suitable quality, and
253        periodically verified as such, for its intended use. Unless otherwise justified, water shall, at minimum meet
254        WHO guidelines for drinking (potable) water quality.
255
256        Special attention shall be given to the design, use, cleaning and maintenance of all equipment for bulk
257        handling and storage, such as tanks and silos [4.9].
258
259        Storage areas shall be designed to protect the products as appropriate and be of sufficient capacity to
260        allow orderly storage of the various categories of materials [4.2].
261
262        Measures shall be in place to prevent unauthorized persons from entering the premises or controlled
263        areas [3.2].
264
265        Defective equipment shall not be used, and shall either be removed or labelled as defective [5.1].
266
267        Piping and devices should be adequately marked and special attention paid to the provision of non-
268        interchangeable connections or adaptors for dangerous gases, liquids and other materials [5.3, 5.4].
269
270        Procedures shall be in place for the operation and maintenance of equipment. Lubricants and other
271        materials used on surfaces that come into direct contact with excipients shall be of the appropriate grade,
272        e.g. food-grade oil [5.6].
273
274        Washing and cleaning equipment shall be chosen and used such that it cannot be a source of
275        contamination [5.7].
276
277 6.4    Work environment
278        Attention shall be given to the prevention of contamination, cross-contamination and mix-ups, through
279        environmental controls, regular cleaning of premises and storage areas, and personnel hygiene practices,
280        especially when excipients are exposed to the environment, e.g. during bulk-handling, sampling or re-
281        packaging activities [3.3, 3.4, 3.5, 4.11, 4.13., 7.2, 7.8]. Storage areas shall be of sufficient capacity to
282        allow orderly storage of materials [4.2].
283
284        A documented risk assessment shall be carried out, commensurate with the operations conducted at the
285        distributor, to determine the necessary controls, including as applicable:
286                 a) Air handling systems shall be designed and operated to prevent contamination
287                 b) the control of special environments,
288                 c) written procedures for the maintenance of clean and sanitary conditions,
289                 d) appropriate identification and segregation of waste if not immediately disposed,
290                 e) freedom from infestation including a pest control program,
291                 f) controls on drains to prevent back-siphoning, and
292                 g) personnel washing and toilet facilities.
293
294        Receipt and dispatch bays shall be equipped with the means to protect materials from inclement weather.
295        Reception areas shall be designed and equipped to allow containers of incoming materials to be cleaned
296        if necessary, before storage [4.3].
297


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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

298   7      Product realization
299   7.1    Planning of product realization
300          The organization shall determine the following, as applicable and appropriate:
301                  e) documented testing programs for quality critical materials that include appropriate
302                      specifications, sampling plans, test and release procedures,
303                  f) environmental and hygiene control programs to minimize contamination of the excipient, and
304                  g) documented procedures describing activities relating to the storage and distribution of
305                      excipients [4.1].
306
307   7.2 Customer-related processes
308   7.2.1 Determination of requirements related to the product
309         Changes requiring notification and/or documented prior approval from the customer shall be determined.
310
311   7.2.2 Review of requirements related to the product
312         No additional requirements to ISO 9001.
313
314   7.2.3 Customer communication
315         The organization shall determine and implement effective arrangements for communicating with
316         customers in relation to:
317                h) significant changes.
318
319          Mechanisms shall exist for transfer of information, including quality or regulatory information, between the
320          original manufacturer and customers [6.6].
321
322          The customer shall be provided with the information on each batch shipped regarding the original
323          manufacturer and the manufacturing site(s) as well as expiry and/or re-test dates.
324
325          COAs that are traceable to the original manufacturers COA shall be provided with each batch shipped.
326
327   7.3    Design and development
328          No additional requirements to ISO 9001.
329
330   7.3.1 Design and development planning
331         No additional requirements to ISO 9001.
332
333   7.3.2 Design and development inputs
334         No additional requirements to ISO 9001.
335
336   7.3.3 Design and development outputs
337         No additional requirements to ISO 9001.
338
339   7.3.4 Design and development review
340         No additional requirements to ISO 9001.
341
342   7.3.5 Design and development verification
343         No additional requirements to ISO 9001.
344
345   7.3.6 Design and development validation
346         No additional requirements to ISO 9001.
347
348   7.3.7 Control of design and development changes
349         No additional requirements to ISO 9001.
350
351   7.4 Purchasing
352   7.4.1 Purchasing process
353         There shall be no upgrading (relabeling) technical or industrial grade material to pharmaceutical grade
354         quality only on the basis of analytical results found in conformance with the requirements of a
355         pharmacopoeial monograph.
356



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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

357          Suppliers of excipients and other quality critical materials (e.g. primary packaging materials) and services
358          (e.g. warehousing or analytical testing) shall be approved by the quality unit after an evaluation of the
359          supplier’s quality management system.
360
361          The quality management system of excipient suppliers shall be assessed by:
362             using the requirements in the GMP or GDP Annex as appropriate to their role in the supply chain,
363             evaluating evidence that they can consistently meet agreed requirements.
364
365          This may include periodic audits of the vendor´s facility. The organization shall require that contractors
366          adhere to the relevant sections of this Annex.
367
368   7.4.2 Purchasing information
369         The organization shall ensure that it is notified by its suppliers of any significant change to the excipient
370         that may impact quality or functionality.
371
372          Any GDP or GMP relevant activity outsourced to another party shall be agreed upon in a written contract
373          including the definition of responsibilities [13.1, 13.4].
374
375          The organization shall evaluate contractor’s compliance with GDP or GMP as applicable. [13.2, 13.3].
376
377          No subcontracting by the contractor shall be allowed unless approved by the organization [13.5].
378
379          Specifications and handling procedures for primary packaging materials shall be established.
380          Relevant storage, handling and safety data shall be available [6.9].
381
382   7.4.3 Verification of purchased product
383         There shall be authorized procedures describing the activities relating to the receipt of materials (e.g.
384         excipients, packaging materials and pre-printed labels) including release of batches for further processing
385         or distribution (see 8.2.3) [4.1].
386
387          Incoming materials (e.g. excipients, primary packaging materials) shall be physically or administratively
388          quarantined until they have been approved.
389
390          Sampling activities shall be conducted under defined conditions, in accordance with a defined sampling
391          plan and method, using procedures designed to prevent contamination and cross-contamination.
392
393          Bulk deliveries shall have additional controls to assure continued material purity and freedom from
394          contamination.
395
396   7.5    Production and service provision
397
398   7.5.1 Control of production and service provision
399
400          Operations, where excipients are exposed to the environment (e.g. combining into a homogeneous batch,
401          repackaging) or relabelled, shall be documented and controlled.
402          Controls shall include, as applicable:
403                   The availability of information that specifies the characteristics of the product.
404                   The mixing of batches to ensure conformance to specification prior and post mixing [7.4].
405                   Ensuring homogeneity when mixing batches.
406                   Line-clearance checks.
407                   Label generating and operating systems and procedures including appropriate verification
408                      and associated records.
409                   Records of use and maintenance of suitable equipment.
410                   The indication of the cleaning status of equipment.
411                   The documented use of quality-critical equipment.
412
413          In addition to the above,
414
415                     All repackaging and relabeling processes shall be designed and carried out to avoid
416                      contamination and mix ups.

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                                         Annex to ISO 9001:2008
                      Additional requirements for GDP for Pharmaceutical Excipients
          based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
              DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

417                    Labels must be applied to each container and be indelible, clear, unambiguous, and
418                     permanently fixed. The information on the label shall be indelible [6.7].
419                 
420                    Repackaging of materials shall be carried out with primary packaging materials (contact
421                     packaging) for which the quality and suitability have been established to be equal to or better
422                     than those used by the original manufacturer.
423                 
424                    Primary packaging material specifications should be established and a written procedure
425                     should clearly define primary packaging materials for each individual excipient based upon
426                     the excipient’s properties and stability.
427                 
428                    The organization shall design and justify cleaning and sanitization procedures and provide
429                     evidence of their effectiveness.
430                 
431                    Equipment and utensils prior to use shall be cleaned and sanitised where their use may
432                     impact excipient quality.
433                 
434                    Records shall document packaging, labelling, cleaning, maintenance and production
435                     activities. Where multi-purpose equipment is in use records shall identify the previous usage.
436
437   7.5.2 Validation of processes for production and service provision
438         No additional requirements to ISO 9001.
439
440   7.5.3 Identification and traceability
441         The original manufacturer and intermediaries handling the material shall always be traceable and the
442         information made available to authorities and end-users, both downstream and upstream [6.5].
443
444         Procedures should be in place to ensure maintenance of the identity and quality of the material by
445         appropriate means, both before and after repackaging operations. These procedures should include
446         documented traceability downstream and up-stream [7.11].
447
448        Batch integrity and traceability shall be maintained and documented [7.2].
449
450         Excipient labels shall include all information required to identify product quality and maintain traceability
451         [6.8]:
452
453   7.5.4 Customer property
454         No additional requirements to ISO 9001.
455
456   7.5.5 Preservation of product
457         There shall be documented storage and handling procedures including protection of container and
458         closure quality to minimise the risk of contamination, damage or deterioration of the excipient and avoid
459         mix-ups.
460
461         A system shall be in place to ensure that oldest materials are sold or distributed first (Earliest Expiry/First
462         Out (EEFO)) [4.12]. The excipient shall be supplied within its expiry and/or retest period.
463
464         Where specific storage conditions are required (e.g. for temperature or humidity) these shall be provided,
465         monitored and recorded [4.7]. These conditions shall be stated on the label.
466
467         Materials should be transported in a manner that will ensure the maintenance of controlled conditions
468         where applicable (e.g. temperature, protection from the environment. The transport process should not
469         adversely affect the materials (12.1). Supplier of transport services shall be provided with the required
470         information in order to maintain required conditions.
471
472         For bulk transport in non-dedicated equipment effective and controlled cleaning procedures shall be used
473         between loadings, and, where appropriate, a list of restricted and/or allowed previous cargoes shall be
474         supplied to the transport companies (12.7)
475


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                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

476          Steps shall be taken, such as tamper evident seals, to prevent unauthorized access to the materials
477          being transported (12.8).
478
479          When containers are to be re-used for re-packaging, effective, controlled and verified cleaning
480          procedures including means of removing previous labels shall be applied. [7.7]
481
482   7.6    Control of monitoring and measuring equipment
483          No additional requirements to ISO 9001.
484
485   8      Measurement, analysis and improvement
486   8.1    General
487          No additional requirements to ISO 9001.
488
489   8.2 Monitoring and measurement
490   8.2.1 Customer satisfaction
491         No additional requirements to ISO 9001.
492
493   8.2.2 Internal audit
494         No additional requirements to ISO 9001.
495
496   8.2.3 Monitoring and measurement of processes
497         The organization shall identify the tests and measurements necessary to adequately control product
498         handling and quality management system processes. Where critical to excipient quality, techniques shall
499         be established to verify that the processes are under control. Where critical to pharmaceutical quality, the
500         organization shall establish an appropriate monitoring programme to show the consistent operation of the
501         excipient handling process.
502
503          Corrective action shall be taken to ensure the excipient meets requirements when critical deviations from
504          planned results occur which could adversely impact excipient quality. The need to notify customers shall
505          be evaluated (see 7.2.1).
506
507   8.2.4 Monitoring and measurement of product
508         Quality documents shall accompany each delivery and facilitate traceability and document conformity of
509         the material to agreed specifications.
510
511          When test results are provided in quality documents received from testing in the laboratory of the
512          organization or by a contract laboratory, the testing operations shall be in compliance with the
513          requirements for laboratory controls in the IPEC-PQG GMP Guide for Pharmaceutical Excipients (section
514          8.2.4.1.).
515
516          Test methods used shall be traceable and comply with agreed standards [7.5, 7.13 ].
517
518          Batch release shall be carried out according to written procedures in accordance with GMP [7.12].
519
520          When product is transferred from one container to another, at least those quality parameters that may be
521          affected by the process, shall be tested for compliance with specification prior to batch release.
522
523          If the organization claims that their product is in compliance with a pharmacopoeia or an official
524          compendium, then:
525                   non-compendial analytical tests shall be demonstrated to be at least equivalent to those in
526                     the compendia, and
527                   the method shall comply with applicable general chapters and notices.
528                   Responsibility for monitoring those pharmacopoeia or official compendium shall be assigned.
529
530          Out-of-specification test results shall be investigated and documented according to a written procedure.
531
532          If excipients are repackaged, processed or packaged from bulk, retained samples representative of the
533          excipient batch shall be kept for one year after the expiration or re-evaluation date or for one year after
534          distribution is complete. The sample size shall be the amount required to perform two complete analyses.
535          Storage conditions of the samples shall avoid any contamination and deterioration [7.14].


        ____________________________________________________________________________________________________________
        Excipient 57157b1a-862d-4b41-895f-f8ef081fa039.doc   22.12.2009                                 Page 9 of 11
                                           Annex to ISO 9001:2008
                        Additional requirements for GDP for Pharmaceutical Excipients
            based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
               DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

536
537          Where excipients are repackaged there should be documented evidence that their stability has not been
538          adversely affected and specified expiry dates or re-test periods are justified [7.15].
539
540   8.3    Control of non conforming product
541          Returned and non-conforming pharmaceutical excipients shall be identified as such and quarantined in
542          defined areas until an evaluation of their quality status has been established by the quality unit(s).
543          Records shall be maintained including the reason for return and the decision made as to the final product
544          disposition [11.1].
545
546          There shall be procedures for the holding, testing, and downgrading of the returned pharmaceutical
547          excipient.
548
549          The organisation shall deal with nonconforming product by one or more of the following ways [11.2, 11.3]:
550               d)    rejection,
551               e)    downgrading to a grade of lower quality.
552               f)    return of the material to the original manufacturer.
553
554          Customer complaints and information about possible defects should be systematically investigated and
555          documented, based on a written procedure with assigned responsibilities [8].
556
557          There shall be a procedure defining how to manage the retrieval of a pharmaceutical excipient. All
558          retrieval processes shall be documented, notified to the original manufacturer and records retained.
559          Retrieved materials shall be stored in a secure, segregated area [9].
560
561          In case of a product non-conformance, an investigation shall be performed to establish whether any other
562          batches are also affected [8.3].
563
564          Corrective and preventive measures shall be taken where necessary and be documented [11.2].
565
566   8.4    Analysis of data
567          No additional requirements to ISO 9001.
568
569         8.5 Improvement
570   8.5.1 Continual improvement
571         No additional requirements to ISO 9001.
572
573   8.5.2 Corrective action
574         No additional requirements to ISO 9001.
575
576   8.5.3 Preventive action
577         No additional requirements to ISO 9001.
578
579
580          Definitions and Glossary
581
582          Distributor(s):
583          For the purpose of this Annex “distributors” includes those parties involved in trade and distribution,
584          (re)processors, (re)packagers, transport and warehousing companies, forwarding agents, brokers,
585          traders, and suppliers other than the original manufacturer.
586
587          Quality Unit (ref: ICH Q7)
588          An organizational unit independent of production which fulfills both Quality Assurance and Quality Control
589          responsibilities. This may be in the form of separate QA and QC Units, a single individual (or group),
590          depending on the size and structure of the organization.
591
592          Organization
593          As in ISO 9001:2008, “organization” is used in this Annex to indicate the entity to which the requirements
594          apply.
595


        ____________________________________________________________________________________________________________
        Excipient 57157b1a-862d-4b41-895f-f8ef081fa039.doc   22.12.2009                                 Page 10 of 11
                                       Annex to ISO 9001:2008
                    Additional requirements for GDP for Pharmaceutical Excipients
        based on the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
            DRAFT FOR REVIEW BY MEMBERS OF CERTIFICATION PROJECT ORGANISATIONS – by 26/02/2010

596       For more details see the IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006 as
597       well as Section 3 of ISO 9001:2008.
598
599       REFERENCES
600
601       IPEC Good Distribution Practices Guide for Pharmaceutical Excipients 2006
602
603       ISO 9001:2008
604
605       Joint IPEC-PQG Good Manufacturing Practices Guide for pharmaceutical Excipients 2006
606
607       IPEC Americas Significant Change Guide 2009
608
609




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