Drug Registration in Botswana

Pharmaceutical Documentation

1. Pharmaceutical documentation should indicate details of:
2. Specification,
3. analytical control procedures
4. release criteria for both raw materials control and finished products
5. manufacturing procedures and in-process controls
6. Stability studies
7. Specifications should include the following details:
8. Title
9. Limits
10. criteria of acceptance of all physical and chemical characteristics
11. Identification
12. Purity
13. Assay/potency
14. Microbiological parameters, where applicable

• Production procedures should include thorough descriptions of every step of the process, including equipment type, in-process control measures, and the packing, labeling, and production phases in the order they are implemented.
• Attached batch production records for the samples that were submitted.
• When other businesses handle different aspects of the production process, such as packing, labeling, quality control, etc., those businesses should be identified and the activities they do should be described in accordance with underlying agreements.

Clinical and Pharmacological Documentation

In the case of novel chemical entities or well-known goods, the Board may consider that pertinent details of pharmacological and clinical information about the drug or a reference to the most recent editions of textbooks or publications on the particular themes should be supplied.

1. Category B drugs

Proof of the formulation’s effectiveness filed for registration will be necessary for Category B medications. Comparative dissolution/bioavailability data, acid neutralizing capability, inhibitory zones, and other measures might be used as evidence of effectiveness.

1. Categories D and E drugs

Drugs in categories D and E need to have their safety and effectiveness thoroughly investigated. These kinds of applications take a lot of effort and often include large amounts of clinical data.

A summary of clinical research for these and other applications, including clinical data, is necessary.

The following details ought to be given:

1. Pre-clinical toxicological data, including research on the product’s safety and its acute toxicity, estimated average fatal dosage, teratogenicity, and carcinogenicity;
2. Details on the medication’s effectiveness, dose, mode of action, and route of administration, studies verifying bioavailability, biological equivalency, and/or the clinical interchangeability of pharmaceutically equivalent drugs.

• Specifics of pharmacokinetic properties, metabolism, metabolic products, and their fate; and

1. Indications, adverse reactions, precautions, and contraindications as may be observed in both humans and other test models.

Status of Registration and Other Information

Registration status in other countries

• The submission of information on the marketing authorization status (registration status) of the medicine in three more countries must be accompanied by certified copies of the relevant certificates.
• Information about the reasons for any deferral, cancellation, or rejection of the drug’s registration or marketing authorization should be provided.

A scheme for certification about the quality of Pharmaceutical Products that are transported internationally

1. The application must be filed with a W.H.O. type certificate in the most recent format, generated in the drug’s country of origin. Only medications authorized for sale in the nation of origin, with a few notable exceptions, would be given consideration for registration.
2. Only nations that do not participate in the WHO certification program will be eligible to submit Free Sale Certificates. But the Good Manufacturing Practice (GMP) certificate should accompany the Free Sale Certificates, and they should contain the same information as the WHO-type certificate.

1. General requirements
2. All the application’s contents should be listed in a table of contents.
3. The application must include a list of sources that were cited. Relevant copies of journals and internal documents should be included whenever they are mentioned.

• Tables and graphs should be used to summarize the data that supports the application. If possible, each application should not be more than 100 pages.

1. Label text matter

Attached should be a sample label that follows the format of the original container and contains the following information per Regulation 8 of the Drugs and Related Substances, Regulations, 1993:

1. Approved name (international non-proprietary name)
2. Brand name, if any;
3. Contents of the container;
4. Quantity of the active ingredient per dosage unit;
5. Batch identification;
6. Expiry date;
7. Storage conditions;
8. Warnings and precautions;
9. Directions for use;
10. Statutory or cautionary label (see Regulation 8(5));
11. Manufacturer’s name and address.

Items (a) or (b), (d), (e), and (f) should be supplied for little containers. This information should be given in an outside container together with the remaining data.

Any advertising or promotional materials must be included with the application.

Additional Information

The accompanying instructions are intended to support MH 2048 Form 1, Application for Registration of a Drug, and help applicants fulfill the necessary conditions for submitting new applications.

1. Number of copies of applications

• The necessary extra documentation and three (3) copies of the registration application dossiers must be supplied. Every submitted MH 2048 document needs to have a covering letter attached. The covering letter should summarize the submission’s contents to speed up the unpacking of the papers.
• The review of the package inserts, labeling information, and application preregistration evaluation may be aided by the provision of MH 2048 material on diskettes or CDs in addition to printed copies. On DRU PCs, Microsoft Office is installed. The candidates are not obligated by this request.

2. Application fees and payment

• P(Pula)800.00 for a drug which imported;
• 00 for a drug which is partially locally manufactured; and
• 00 for a drug which is totally locally manufactured.

3. Multiple manufacturing sites

• The applicant must list all potential producers of the medicine for which they are applying, and they must ensure that each manufacturer has completed the Company Registration Form and is registered with the Drugs Regulatory Unit. Attached should be the GMP certifications for every manufacturer.
• A duplicate of the application for business registration that Botswana Central Medical Stores has received is valid.

4. Storage Conditions

• Storage conditions should not just include descriptive language; they should also represent actual storage temperatures, both with and without such terms. “Store at room temperature below 30 °C,” for instance Do not “Keep at room temperature.”

5. Immediate container

• The immediate container is the main container that comes into direct touch with the medication and any other secondary containers or closure systems essential to maintaining the product’s integrity.

6. Samples

• Samples that are sealed and contain at least two (2) batches, together with certificates of analysis, should be presented in the actual distribution container. Each sample should have enough to allow for at least three full monograph tests (per the requirements).

7. Raw material sample

• If possible, a certificate of analysis and a fair quantity—roughly 10g of standardized active raw material—must be supplied with the request.

8. Batch production records and release certificates

• At least two batches’ worth of batch production records (BPR), which match the samples (see the section above titled “Samples”), must be sent in. All entries made throughout the production process will be reflected in these. On the BPR, cancellations must be countersigned and kept readable. Correcting fluid usage is not permitted. A translation of the relevant record must be supplied if the entry form’s framework is not in English. Only materials that can be clearly photocopied will be accepted.
• All raw materials must have certificates of analysis included;
• All vaccines, biological, and biotechnology products must have batch certifications presented.

9. Stability Studies

• It is required to submit a thorough report of investigations from a minimum of three (3) batches (attached to page 5 of 7 of MH 2048 Form 1, “Pharmaceutical Documentation”).

1. Only real-time research under suggested storage conditions will be approved for all items made entirely abroad.

10. WHO Type Certificates and Free Sale Certificates

As Product Certificates, only those that align with the most recent version of the World Health Organization Certification Scheme on the Quality of Products Moving in International Commerce will be recognized. Certificates of Free Sale from nations that participate in the WHO certification program will not be accepted.

11. Promotional material

Submission of copies of both current and proposed promotional materials is required.