Quality and Storage of TB Drugs in Potchefstroom South by jhr80137

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									Quality and Storage of TB
Drugs in Potchefstroom
South Africa
Johanita Hendriks (South Africa),
Erasto S.T. Mosha (Tanzania),
Steven Chapima (Malawi),
Kayini Chigayo (Zimbabwe),
Arminda Banze (Mozambique)
   Overview & Introduction
• At Potchefstroom University (CENQAM) a
  course took place sponsored by CDC & WHO
  on use of TLC and TB Drug Quality
• Attended by participants from RSA,
  Zimbabwe, Mozambique, Zambia, Malawi,
  Tanzania & Kenya
• Learnt about the use of TLC for TB drug
  Quality
• Undertook field visits to observe storage
  conditions and to collect specimens
• Tested samples coming from all countries
                                              2
Objectives
• To introduce basic TLC principles and
  practices
• To describe a simple and cost effective
  method to screen pharmaceutical products
• To collect and analyze TB drugs from
  Potchefstroom area
• To report results to national, provincial & local
  TB staff and pharmaceutical specialists

                                                  3
     Background   1

• 8 million cases of
  TB in world today.
  Number increasing!
• According to WHO, South Africa is the
  8th worst in the world in terms of
  incidence with an incidence rate of
  437/100K
• Second only to Zimbabwe in terms of     4
  combined burden of TB and HIV
      Background 2 TB in South
      Africa
• For South Africa in
  1999/2000; 236,000         1987
                                      1998
                                                  2015


  new cases expected
• 90,000 sputum
  positive (INFECTIVE!)
• If current trend continues will result in 3.5
  million new cases over the next decade
  and 90,000 additional deaths per year                  5
Background 3 - North West
Province TB Situation
• Incidence 1995 was 143 per 100K
• Incidence 1996 was 178 per 100 K
• Cure rates in 1997 were 30% (Dept
  Health & Developmental Social Welfare)
• Situation improving 1998 & 1999 cure
  rates were 52%


                                       6
         Background 4 Outcomes of Treatment
         in Potchefstroom area 1995-96

                    60                   59.6



                    50
                         48.9


                    40

                                                                                         Protocol 1
            %
                                                 26.3                                    Protocol 2
         Patients   30
                                         22.2                              20.6

                    20
                                                           11.5                   12.3


                    10
                                                                  1.8

                    0
                          Successful   Unsuccessful     Not TB          Unknown

                                         Treatment outcomes
                                                                                                      7
New protocol now in use since Oct 1999
Background 5 - TLC as a Primary
Screening Tool for Drug Quality

• TLC used qualitatively for 40+ years
• TLC used for quantitative measures
  since 1960 using comparison of spot
  intensities with reference standards
• Found to be faster, of low cost and
  lesser degree of technical expertise,
  and much cheaper with less pollution
• Mini method developed by Kenyon and
  Layloff in early 90’s                   8
Methods 1 -Sample Collection
• Combination of random selection and
  convenience sampling used
• At hospital, specimens collected from
  pharmacy store, not bulk store.
  Collected both old and new batches
  Total of 9 drugs
• At clinic, collected 7 specimens using
  convenience sampling because few
  specimens
                                           9
 Methods 2 – Logging and
 Coding Specimens
• Logged in register as “First come, first logged”
• Recorded manufacturer, Lot No, Expiry date,
  Trade name, dosage form, & active ingredients
• Allocated code number based on generic name
  to each product to ensure “blind” testing
• For combination products used first letters e.g.
  RI for Rifampicin and Isoniazid or REP for
  Rifampicin, Ethambutol & Pyrazinamide

                                                 10
Methods 3 –Assay Methods
•Thin Layer Chromatography according to
method of Kenyon & Layloff
•Confirmatory method was by UV
spectrophotometer
•Dissolution testing was not undertaken due
to time constraint




                                              11
         Results 1- Collection Results
         Hospital
         • At hospital collected 9 specimens*
         • Good storage conditions with frequent
           reorder
         • No formal stock control system at present
         • Drugs which should be out of system were
           still available
         • Security appeared lacking
         • Very good pre-packing system with QA and
           recording system
                                                                      12
* two more than expected INH + Thiacetazone & Injectable Rifampicin
Results 2- Collection Results
Clinics
• Collected from 2 clinics (6 from Top City
  and 5 from Boiki Tlhapi)
• Storage conditions were good
• Stock control system working but Lot
  No.s not recorded
• Returning excess stock to hospital is
  very impressive!!

                                          13
     Results 3 - TLC Analyses
       Drug   Rif       INH    PZA       Eth
                                     Method Failure
       RIE    OK       OK+      -
                                       Not Done
       REIP   OK         OK    OK
      I&Thia           OK*
       Strep More than 115%
        RI    OK       OK ?-
       RIEP   OK         OK    OK+     OK+
* Thiacetazone observed                           14
Discussion 1
• Useful for lab analysts to collect field
  samples
• Impressed by availability and storage
  conditions of TB drugs
• According to TLC, TB drugs of good
  quality
• TLC useful screening tool for TB drug
  quality
• Dissolution should also be done as a
  complementary screening test (not done   15
  for SA specimens)
Conclusions and Recomendations
• TLC can be used successfully in
  screening and monitoring TB drug
  quality
• Based on TLC results, no evidence that
  poor cure rates are due to low drug
  quality. BUT dissolution not tested!
• We recommend that TLC screening be
  undertaken before any more expensive
  final testing                         16
References
Tuberculosis Problems in the North West Department of Health and
   Developmental Social welfare 1997 Mmabatho
Weyer K. Fourie PB, Nardell EA Noxious Synergy: Tuberculosis and HIV in
   South Africa Soros Foundation 1999
Course Notes on Methods for Sampling
Kenyon A.S. & Layloff T.P. Rapid Screening of Pharmaceuticals by Thin
   Layer Chromatography FDA (no date given)
Kenyon AS, Zuzack J., Patel R, & Le V Cost sparing analyses using a rapid
   scanning thin layer chromatographic method Pharmacopeial Forum
   24 5 6607-6611



                                                                            17
Results 4 - UV Analysis
       Drug         Rif UV Result
        Rif                103.3
        RI                110.11*
        RI                100.34
        RI                121.03*
     Rif Syrup             90.4
                                    18

								
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