Quality and Storage of TB Drugs in Potchefstroom South Africa

1
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)

2
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

3
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

4
Background 1

• 8 million cases ofTB 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 combined
  burden of TB and HIV

5
Background 2 TB in South Africa

• For South Africa in1999/2000 236,000new 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

1987
2015
1998
6
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

7
Background 4 Outcomes of Treatment in
Potchefstroom area 1995-96
New protocol now in use since Oct 1999
8
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 90s

9
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

10
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

11
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

12
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

two more than expected INH Thiacetazone
Injectable Rifampicin
13
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!!

14
Results 3 - TLC Analyses
Thiacetazone observed
15
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 for SA
  specimens)

16
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

17
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

18
Results 4 - UV Analysis