Procedure and Outcome of Prequalification of Medicines Program by World Health Organization (WHO)

In March 2001, World Health Organization (WHO) Prequalification of Medicines
Program (PQP) comes in action...


Introduction
Quality of medicines is always a problem in countries where regulatory and legal oversights are weak, medicines are not affordable to most and where often patients do not get medicines.
To ensure effective treatment, to maintain patient and health-care worker confidence in treatment, quality is important. Additionally, it is also important to prevent development of resistance. As a realization of the fact, in 1977, the World Health Organization (WHO) published the first Model List of Essential Medicines (Essential Medicines List, EML). The EML assisted health authorities in selecting products for primary healthcare. It introduced the idea that some medicines are more important than others. Many later considered the first EML 'a revolution in public health' [1]. is to contribute to the priority goal of United Nations which is to address common diseases in countries that have limited access to quality medicines [2]. Continuous improved quality of life saving medicines used by thousands of people in developing countries is the greatest accomplishment of this program.

Activities of Prequalification of Medicines Program (PQP)
There After discussion with WHO disease programmes and/or clinical specialists, this EOI is issued by WHO [3]. Generally, medicines that are identified as vital by WHO clinical experts for effective and development of treatment programmes or to safeguarding reproductive health are invited for evaluation. WHO Model List of Essential Medicines or Medicines for Children, and/or WHO treatment list or other relevant guidelines mainly enclosed all the medicines listed in the EOI. Although, there are some exceptions, such as medicine may not include in the model list of essential medicines and/or treatment guidelines are yet to be considered a vital for meeting treatment necessities and invited for assessment [3].

f)
Product for the treatment of maternal and child health. g) Product for the treatment of neglected tropical diseases.
h) Product for the treatment of reproductive health.

i)
Product for the treatment of tuberculosis (Table 1).

APIs Eligible for Assessment [3]
APIs used to formulate medicines that are incorporated in the

i)
Product for the treatment of tuberculosis. The following is a simplified overview of the APIs and FPPs prequalification process. Firstly, the API or FPP must be included in the relevant invitation to manufacturers to submit an EOI for

Procedures for Prequalification
Evaluation. Secondly, in accordance with the prequalification procedure manufacturer submits an application for the product (either API or FPP). After that, a screening checklist is used to check the submitted application for prequalification by WHO. They may ask for additional information after screening. Key elements of an evaluation of generic FPP are the insight of screening checklist. If the submitted dossier satisfies the screening requirements, then a reference number is assigned and accepted for full evaluation.
Then, abbreviated assessment procedure may be followed by the applicant for the API or FPP that already been registered by

Assessment Procedure of FPP
There are two procedures for FPP prequalification. Each procedure has specific submission requirements. a) Full assessment and b) Abbreviated assessment.

Full Assessment Procedures [5]
In order to be prequalified, a multisource (generic) finished September 2011, long term stability data at Zone IV conditions (30°C/65% for IVa or 30°C/75% for IVb, respectively) and in some cases, at Zone II (25°C/60%) data was accepted. Now-a-days, WHO expect all prequalified medicines will be used in all sub zones of III and IV unless justified by the applicant (Figure 3). Therefore, in order to maintain product quality throughout its entire shelf life, stability study need to be performed at climatic zones IVb. Based on complete long-term data at 30°C ±2°C/75% RH ±5% RH as required during dossier submission, the shelf-life should be established [8,9] ( Figure 3).

Bioequivalence [10]
Standards between Multisource (generic) products and originator or comparator products must be same. Generic manufacturer must ensure their products are of: 1. Same quality standards as those applicable to the comparator product 2. Therapeutically equivalent or bioequivalent to the comparator product  QIS-SRA template, available at website (http://apps.who.int/ prequal/).

Submission Procedure [14]
It consists of two steps: a) Step 1: Submission of documentation for the purpose of screening: Pictorial presentation of this step is provided in Figure 5.

b) Step 2: Document submission
After applicant received a confirmation email or letter from WHO that, the dossier has been accepted for evaluation and a reference number assigned for its submission can be made [14].
Pictorial presentation of this step is provided in Figure 6.   the dossier along with a Letter of Access from API manufacturer that provide WHO prequalification team to review the restricted part (RP) of APIMF. FPP manufacturer need to ensure that the API manufacturer provide the required documents as requested by the agency for review. APIMF reassessment usually not required but "acceptability" of API manufacturer will always be reviewed as part of FPP prequalification (Figure 7).

A. Prequalification of Quality Control Laboratories
To meet the standards of quality and safety of FPPs and APIs

Site Inspection
Planning and coordination of site Inspection of API and FPP and clinical testing units or CROs will be done based on a) SOPs. b) Quality risk management (QRM) principles [7].

Outcome of the Prequalification Procedure
WHO will publish the evaluation report named "WHO Public Assessment Report (WHOPAR(s))" for the product dossier and inspection reports called "WHO Public Inspection Reports (WHOPIR(s))" for manufacturers of API & FPP and CROs, if they comply with the set standard [21].

Fees
From 1 st January 2017, a new fee schedule has been published by WHO API, FPP and Vaccines. This new fee schedule will be monitored, and assessment will be done for 03-year time [22] ( Table 2).  and Quality Control Laboratories (QCLs) ( Table 3).

Laboratories (QCLs)
No validity (Prequalified APIs are not subject to requalification, but certain requirements must be met if prequalification status is to be retained) 05 years 03 years

Conclusion
Prequalification program of WHO is a renowned and broadly recognized tool, which acts as a self-regulating body and represents a sole global system. It ensures quality, safety and efficacy of priority medicines as per international and unified standards. The main role of WHO-PQP is to facilitate access for under privileged to get quality products. It also plays an active role to build up capacity with national regulators, QCLs and manufacturers.