Control of Veterinary Drugs in South Africa By Prof Naidoo . MMALENCOE MOROE-RULASHE DAFF-SOUTH AFRICA.

Veterinary Drugs: SA South Africa is a closed market All products require authorisation for Sale Manufacture Wholesaling Importation Exportation Bonding Utilisation

Two General CATEGORIES Prescription Only Act 101/65 Veterinary Medicines Antibiotics Anaesthetics Sedatives Analgesics etc Over the Counter Act 36/47 Stock Remedies Parasites Tetracyclines Growth Promoters Vaccines Supplements

Act 101/1965 The main control act in South Africa Controlled by DoH: SA Health Products Regulatory Authority (SAHPRA) Controls by means of schedules S0-S2: Over the counter (Human) S3-S6: POM (Prescription Only Medicines) S7-S8: Prohibited

Act 36/1947 Governs the use of stock remedies, agricultural remedies and feed (feed additives) Controls by means of access Sale from open shops Limited sale (Vet only)

Why the need for two acts Allow farmers access to certain drugs Act 36/47 promulgated under agriculture Only 3000 vets in SA, with 100 practices dedicated to productions animals Medicines Act promulgated later Vet POMs 1983 (Old Medicines) Under Department of Health Problems controlling an Act in another department

Further Control Food Safety: Foodstuffs, Cosmetics and Disinfectants Act Vaccines: Animals Diseases Act Environmental Protection: Hazardous Substances Act Professional Acts: Veterinary Act, Pharmacy Act, Health Professions Act Consumer Protections Act Advertising Standards Authority Animal Ethics: SA National Standard 10386

Pillars of control All products are evaluated. No mutual recognition on registration (Except Manufacture) Safety Preclinical, clinical and environmental Quality Manufacture quality Efficacy Target species Target indication

Safety Preclinical Safety Laboratory animal toxicity testing OECD GLP Accept OECD guidelines (SANAS) Companion animals Vs Production Animals Food safety, ADI and MRLs Accept CODEX MRLs

Quality Agriculture Health GMP approval: Major Regulator’s Approval In-house evaluations Health Inspectorate evaluates all manufacture facilities Internal or via PICs (WHO cGMP) Frequent monitoring Wholesale and storage sites Vaccine quality laboratory (Medical) No analytical laboratory (pending) Batch release (ISO17025 Accredited labs)

Efficacy Quality Control: GCP (MCC or SANAS) Statistical designed studies VICH guidelines WAAVP protocols Bioequivalence acceptable AUC (80 to 125%); Cmax (75 to 133%) Local Studies Parasiticides, Mastitis Remedies Require regulatory and ethics approval

Food safety Compulsory for all products Except pharmacokinetic bioequivalence Depletion study or single time point Per species and route At maximum recommended dose Evaluated against CODEX or EU MRLs Law does allow for setting of MRLs Not commonly undertaken except pesticides National and commercial residue laboratories

Pharmaceutical Full technical dossier required All manufacturing information All ingredients Quality (Chemical/Biological) Mixing process GMP compliance Stability: Accelerated and actual Zone II and some in Zone III Packaging

Package inserts/Packaging Major attention to editing PI Veterinary Medicines Based on the clinical and tolerance data submitted Template PIs considered Owner Information Leaflets (In discussions) Stock Remedies Emphasis on language No complicated instructions or information Well designed packaging

Pharmacovigilance Spontaneous Reporting Comprehensive guidelines Veterinarians and applicants obliged to submit No vet pharmacovigilance centre Controlled by each Department Applicants Have to have a technical expert on staff (Vet) PSUR evaluations requested on concern NSAIDs Antimicrobials

Inspectorate Both Departments Hospital and practice inspections (Health) Monitor all ports of entry (Via customs) Border Control Agency (To be set up) Stricter control on chemical imports Monitor internet sites (Health) Illegal products Assisted by local pharmaceutical industry National labs: Jockey club, Forensics, SABS, Doping, Residue, WHO reference lab Non-compliance with certificate of registration Illegal marketing/Sale Complaints/Pharmacovigilance

Sa legislation: differences Minor species, minor use Still in process (e.g. fish) Used for wildlife immobilisation agent Mastitis Guidelines (Done) Unique SA bacteria Unique conditions of use Complementary and alternative medicines Controlled by health Strict control on manufacture No specific claims allowed

SA deficiencies Insufficient experts Insufficient Inspectorate Not training new experts Insufficient Inspectorate Insufficient Quality assurance laboratories Compounding of veterinary medicines Meant for limited use Control as pharmacy and not manufacture No clause in law to restrict quantity Dual regulatory system? Difficult to maintain uniformity in process Plans: Harmonise guidelines/implementation

Conclusion Future Plans to assist in VMPs activities Streamline process/ Uniformity Control of all VMPs under/by one Authority? New Authority which replaced MCC SA Health Products Regulatory Authority (SAHPRA) Control human foods, medicines, medical devices, complementary medicines, Vet POMs Inclusion of OTC: Stock remedies: Under discussion Mutual recognition in SADC SA experts involved (Health and Agriculture) Proper Standard Proper Evaluator Qualification VICH Involvement