South African CMC Compliance

Pharmaceutical companies can thrive in South Africa owing to the legislative framework for regulation of medicines and a burgeoning market for unmet medical need among sufferers of HIV/AIDS and those inflicted with other infectious diseases. If drug companies intend to take advantage of the market opportunity and deliver medicines to patients, they must firstly focus on the effective lifecycle management of medicinal product registrations. In South Africa, post-approval maintenance is achieved under a change classification system of type A, B and C amendments, with the quality and performance of a dosage form that influences the filing mechanism.

The 730 day approval timeline for a change, harmonization of dossier content to common technical document (CTD) format by 2016 poses a big challenge to chemistry, manufacturing and controls (CMC) regulatory professionals. CMC professionals must collaborate with all stakeholders including regulatory affairs, manufacturing, supply chain and marketing to achieve compliance of product portfolios in this market.

The Republic of South Africa is the largest market on the African continent and is a member of the “BRICS” group of emerging world economies. It has a population of 51 million and a gross domestic product (GDP) of $384 billion in 2012.

Life expectancy at birth is quite low 57 years and 60 years for males and females respectively in comparison with other nations. The standard of care offered in the public and private healthcare systems in South Africa is inconsistent leading to a disparity in the over-stretched public health sector. The nation’s government hopes that people will adopt private health insurance policies, in order to reduce the burden on the state.

South Africa and the African continent are plagued by the HIV/AIDS virus, the Department of Health in South Africa is working towards combating the spread. It is estimated that 5.4 million people over the age of 15 are carrying the virus in South Africa, which is also tackling other infectious diseases such as cholera and malaria.

South Africa’s regulatory agency, the Medicines Control Council (MCC, “the Council”) assesses applications for new product registrations and post-approval amendment applications. In South Africa, a change to a registration dossier is known as an “amendment”, which is further classified into categories “Type A”, “Type B’ or ‘Type C’ and “Type D’, which is used for new applications. Nature of the amendment which will impact the quality or performance of a dosage form will dictate the category in which it is evaluated. It will also determine the filing mechanism, the approval timeline (if any) and the documentation requirements that must be met.

Opportunities and Future Outlook

Companies possessing pharmaceutical product licences in South Africa must convert their dossiers from existing format to the South African CTD (ZA CTD). Since 1 July 2010, the applications in ZA CTD format have been accepted and MCC has set a deadline of 1 June 2016 for harmonization of all dossiers.

The ZA CTD structure is based on ICH M4Q guideline and there are minor differences in naming conventions for e g; the 3.2.P.4 section is known as “Control of Inactive Pharmaceutical Ingredients” as opposed to “Control of Excipients”. The ZA CTD file is similar to an EU dossier in terms of content than the US dossier. For a CMC regulatory professional with respect to older products that may have seen a relatively low level of CMC change, conversion to the ZA CTD (less similarity in terms of section granularity to the previously used Medicines Registration Form (MRF1) represents an enormous volume of work.

The CMC regulatory professional must undertake a complete re-write of the dossier, to include the registered information under the relevant CTD sections. Alternatively, a contemporary dossier can be supplied, and a thorough gap analysis against the current file must then be undertaken and followed up with any necessary remediation actions, which may include the filing of “missing” amendments. Both approaches are time-consuming and require due diligence and attention to detail, however the CMC function must focus on achieving fully compliant dossiers which are reflective of current manufacturing practice.

Regulatory professionals engaged in CMC lifecycle activities in South Africa face such pressing challenges like lengthy approval timelines for major variations and full conversion of product dossiers to the CTD format.

In addition, HCR’s have a long standing goal to achieve CMC regulatory compliance across the entire product portfolio. It is imperative to understand the regulatory requirements to deliver the CMC submission packages and human resource must be managed to meet the harmonization deadline in 2016.