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NMRA gives marketing authorization for medicine, medical devices, borderline products and cosmetics. NMRA has procedures for the approval of local manufacturing sites relevant to all above product types. NMRA also requires approval of overseas manufacturing sites of medicine and medical devices, before proceeding to accept application for marketing authorization of individual products manufactured at these sites.
Legal provisions for the site approvals are provided in sections 49 (2), 51, 75 (1), 96 (1) (a) and (3), and 113 of the NMRA Act No. 5 of 2015. The approval process for overseas manufacturing sites of medicine is described in regulations 2 (3) to 2 (10) of Part I of medicines regulations No. 2145/1 of 14.10.2019. Regulations 26 to 30 of Part II of medicines regulations applies for local manufacturers of medicine.
The process applies for local manufacturers of medicine, medical devices, borderline products and cosmetics. The procedure involves review of essential documents including the Site Master File and several rounds of GMP audits by the Authority.
The initial step for a new local manufacturer is to submit an application for preliminary approval of a new local manufacturing site along with copies of documents listed in the application, which include the following:
When setting up a new plant, adhering to the following basics will assist the approval process:
The approval of a new site is a step by step process and may include the following stages:
The above is a tentative roadmap for a manufacturer of medicines and may vary for other product categories and there may also be follow up inspections if there were deficiencies observed during a particular inspection.
The process applies for overseas manufacturers of medicines and medical devices who intended to get marketing authorization for their products in Sri Lanka. The procedure includes a desk review of essential documents including the site master file. A GMP inspection of the site may be necessary before approval of the site.
A foreign manufacturer who wants to register products in Sri Lanka needs to appoint a Sri Lankan business entity as its local authorized agent. The local agent will furnish an application for approval of an overseas manufacturer of medicines on behalf of its principle company, the foreign manufacturer. A separate application needs to be submitted to each manufacturing site from which the manufacturer plans to export products to Sri Lanka. A processing fee as per the fees regulations of NMRA will be charged for each application.
If the manufacturer fulfills all the requirements indicated in the application including documents submitted with the application, the next step would be to carry out a GMP inspection of the facility. The NMRA would exempt the onsite GMP inspection if the particular site had been inspected by a reference NRA or WHO, in terms of regulation 24 of the medicines regulations. After these procedures, an approved foreign manufacturer can submit application for marketing authorization of individual products through the local agent.
A Site Master File is a set of documents required to be enclosed with applications for site approval which provides NMRA a description of the manufacturing site with regard to premises, personnel, processes, documentation, equipment used in the manufacturing, processing, packaging, quality control , storage, distribution, complaint handling and recall of Medicines, Medical Devices, Borderline products and cosmetics.
References:
Good manufacturing practice (GMP) is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.
The National Medicines Regulatory Authority Act No. 5 of 2015 interprets GMP guidelines as ‘good manufacturing guidelines issued by the World Health Organization’. As such, the National Medicines Regulatory Authority (NMRA) adopts the WHO GMP guidelines along with its subsequent updates for the purpose of regulation of pharmaceutical manufacturers. The manufacturers are expected to adhere to the Good Manufacturing Practices throughout their activities.
Pharmaceutical manufacturers who intend to apply for marketing authorization in Sri Lanka may be subjected to one or several GMP inspections prior to their site approvals.
Useful guidelines published by WHO can be accessed through the following links:
WHO TRS 996 – Annex 3: WHO good manufacturing practices for biological products:
https://www.who.int/publications/m/item/trs996-annex3
All pharmaceutical manufacturers are required to conform with the Guidelines on Good Manufacturing Practices of NMRA, which consists recommendations of the World Health Organization (WHO) relevant to GMP. NMRA conducts pre-approval and routine GMP audits on local manufacturers in order to assess them for conformance to GMP standards. Overseas manufacturers are inspected at the time of approval or if there are consistence and/or serious issues such as quality failure of products. Fees for both local and overseas GMP audits are charged as per the fees regulations of NMRA.
The composition of the GMP audit team will be notified to the company via email, after the relevant payment is made. The GMP audit team will request for an updated Site Master File for a pre-audit assessment of the site. The lead GMP auditor will discuss with the company for dates for the audit and will inform of the tentative audit agenda.
On the first date of the audit, the GMP audit team will meet the key personnel of the manufacturer, introduce themselves, and give a brief description of the purpose of the visit and scope of activities. Then the manufacturer will be requested to present an update of the site and any recent significant changes, if any such as changes to key personnel, equipment and facilities etc.
The team will proceed with the audit of the plant and observations will be recorded. During the audit, the team will review previous non-conformities and corrective actions taken to rectify them. The manufacturer shall arrange a meeting room for the review of documents requested by the team.
After completion of the audit, a closing meeting will be held and the audit team will present a summary of observations. The audit ends after the closing meeting.
An inspection report along with a post-audit letter will be send to the manufacturer in which the non-conformities will be listed as critical, major, and other deficiencies. The manufacturer is expected to respond to the non –conformities observed with time frames required for correcting them. If necessary the audit team will make a follow up visit to audit the implementation of the corrective actions.
If the audit team is satisfied with the corrective actions and time frames for rectification, the audit will be closed out. The due date for the next audit will be determined using a risk assessment system. In general, re-inspection of ‘high risk’ manufacturers (e.g. manufacturers of sterile products) will be more regular.
List of approved local manufacturers of medicine (table)
National Medicines Regulatory Authority,
State Engineering Corporation Building (2nd Floor),
No. 130,
W.A.D Ramanayaka Mawatha,
Colombo 02,
Sri Lanka