SUPPLIERS QUALIFICATION

Transcription

1 SUPPLIERS QUALIFICATION With each passing day, new suppliers and manufacturers of packaging materials, raw materials, laboratories, etc., appear, offering products and services of different quality levels. It is, therefore, of paramount importance that the company have a robust Evaluation Program Suppliers in order to maintain then quality of products being manufactured and reduce the sanitary risk. The qualification program may include suppliers of Raw Materials, Finished Products, Packaging and Labels. The application of this Qualification Program does not ensure, by itself, the qualification of the supplier and the absence of failures. The acceptance of the results of evaluations, accreditations, selections, and possible third-party certification, are under the responsibility of the purchasing companies and contractors. In other words, they can decide negotiations regardless of the results of this process. Certification programs do not exempt companies from committing faults, errors, but show, clearly, their attitude towards their customers, to fix, in a corrective and preventive manner, all non-conformities. Tool For Management Qualification As ICH Q9 In Supplier The use of the tool " Ranking and Filtering" (RRF) in the pharmaceutical industry began in early 2002, when the FDA noted that, due to the increasing number of laboratories, it lacked the resources necessary to perform the routine inspections that were programmed. So it was essential to establish a methodology for risk analysis to prioritize inspections, i.e., define which laboratories should be audited in the first place, according to the risk of its activities involving public health. The method of " Ranking" can be defined as a risk analysis tool that enables the comparison and evaluation of the risks. If the Filtering is added to this method, a filter will be applied which will serve to define the framework of actions, about which risks should be acted upon. Objective The objective of this method is to obtain a list of the risks assessed and arranged according to their criticality. Once the list is prepared, the decision will be based on resources that are available, which indicate the risks that can be reduced. Application The application of this method is recommended when performing a risk analysis on a system with very different risks among themselves and with consequences that can be very different as well. For example, it may be helpful in Planning Audits (for manufactures for third parties, manufacturers of active ingredients, laboratories, etc.), Training Plan, Validation Master Plan, Review of Product Quality, Calibration Plan, etc. Advantages and Disadvantages Advantages: - Allows you to prioritize actions to reduce risks; - Useful when very different factors are inserted in the risk assessment; - Widely-accepted in Health Audits; Disadvantages: - There must be a good explanation for the "filtering". For example, audit the manufacturers IFA with an RV> 12; - It should be revised with an established frequency. The listing (or ranking) varies according to the actions perfomed to reduce risks;

2 Operation of an RRF The operation of an RRF can be summarized as follows: Identificarion Evaliation Ranking & Filtering Ranking Matrix Filtering Matrix FILTER RANKED LIST 1. Identification Similarly to other methods of analysis, it is first necessary to identify the risks. In order to perform this stage of RRF, a brainstorming session is desirable,, where different people from the company can show the related risks. A good way to start a brainstorming session can be a set of several questions to the people who are supposed to identify the risks. Once the risks are identified it is convenient to group them by categories, for example: - Quality System; - Analytical Results, - Manufacturing plant single-purpose or multi-purpose. - etc. These groupings are called risk factors. It is recommended that the risk factors meet a number of requirements for the model of RRF to be consistent:

3 Logical Consistency Compatible with the organization and legislation Equality Exhaustive list, not to leave out any relevant risk; The resulting priorities should be easily interpreted by the management; The number of factors considered must be enough to meet the GMP rules in detail and not to create questions during the inspection; Compatible with the existing database in the organization to facilitate the information search; The factors considered should well represent the interests of the various parts affected. This is reflected especially in the selection of the "weights"; Compatible with the "company culture". The factors chosen should be easily assimilated and familiar; Factor Factor 1 (WT) Level of Score Description Factor 2 (WT) Example of allocation table values Each risk factor (or risk value) for each item corresponds to each element analyzed or risk factor by level of risk associated with one of the parameters. The risk associated with a part of the system will be the sum of those products, as represented in the following formula: Logical Structure Should not be too many analysis is not very complex; so the Avoid categorizing better (many sub-factors) the best known and worse the more unknown; it must be homogeneous. 2. Evaluation To conduct the risk assessment system, you must first assign the values of each risk factor. Once analysed all risk factors, each score is multiplied by the weight factor associated with the relative Effective Score. The final score ( Level) is obtained by summing the actual points of each risk factor. It is recommended that the weights add up to a 10 or 100 etc. in order to easily justify the % assigned to each one. Each risk factor is assigned to a numerical value called weight. Since all risk factors do not have the same importance, this value can be used. For example, in an evaluation of suppliers of packaging material, the risk factor "Quality System ISO" should have a higher weight than the risk factor "Geographical location of the supplier", because the former represents a greater risk of receiving or not the packaging material in conformity. Each risk factor may be subdivided into different levels of risk. In the previous examples, you can assign a score 1 ISO 9001/14001 is presented, a score 2 if only an ISO certification is presented and 3 there is not any ISO 9001 certification. A table can be created (or risk matrix) which will serve to list each item or part of the system with the assigned values: Item Item 1 Item 2 Item 3 Factor 1 Factor 2 3. Ranking & Filtering Factor 3 Value (RV) Comments The last step of this analysis method is to list the items according to the risk value obtained from the highest to the lowest value (ranking), so it is possible to prioritize the risks

4 of higher value and make sure that the items with higher value are treated first. If there are no resources to act on all items, it must be decided which risk will be the first to receive an action. They will probably be those on the top of the list by applying the "filtering". Below is an example of a table containing the end result of a " Ranking": Kind of material (IFA, packaging.) Manufacturer Value IFA X 25 IFA Y 28 IFA Z 32 Because companies do not have a sufficient number of professionals to perform all audits, audits with less " Value" are postponed to the following year Acquisition of relevant information about the supply chain for the Packaging and Raw Materials Approval of suppliers of packaging materials or raw materials Permit for the specification of packaging material or raw material Packing material or starting bought and used in the manufacture of finished products Analysis and trends of results Qualification of the supplier of packaging materials and raw materials Product Periodic Review The audit plan for the next year should take into account the suppliers / manufacturers who were previously excluded from the audit plan. A risk factor that represents the time elapsed since the last audit or if the audit could not be performed according to a previous audit plan c can be inserted into a table by assigning values. Supplier Qualification Process The qualification process for suppliers of packaging materials and raw materials can be designed in a sequential flow of activities as follows: Understanding the nature of the packaging material or raw material Understanding the nature of the finished products Acquisition of relevant information on the packaging or manufacturer of raw materials 1. Understanding the nature of the packaging material or raw material The nature of the packaging material or raw material may have impact on the type and quantity of information being requested from a supplier at the time of qualification. If the packaging material is a pre-printed material, primary or secondary component. If the raw material is a pharmaceutical excipient active ingredient or bulk. In compliance with any international standard ( e.g., BP, USP). Specif grade of the material to be used and its physical critical properties If the material is of human, animal or biological origin. 2. Understanding the nature of the finished products The nature of Finished Goods that are used in packaging materials and raw materials may

5 present an impact on the type and quantity of information that will be requested to a supplier at the time of qualification. The type of medication (e.g., non-sterile, herbal medicine). Identification of potential consumers of the finished product. Other ingredients that can be used in formulations of finished products. Any potential stability issue regarding the finished product. Any potential manufacturing issue regarding the finished product. Considerations of the nominations of the finished product and label. Identification of the dosage instructions of the finished product. 3. Acquisition of relevant information about the manufacturer of the packaging material or raw material The acquisition of relevant information, including the identification of the manufacturer of the packaging material or the raw material, is necessary to achieve the qualification of the supplier. It may not be possible to deal directly with the manufacturer of the packaging material or raw material. If this occurs, it may be possible to obtain information about the manufacturer through their supplier. A questionnaire or a standard form to collect this information may be used. A copy of the Site Master File from the manufacturer can be helpful. This information can also help the risk assessment which should be conducted before adopting the reduction test / analysis. The place of manufacture of the material and alternative sites used. The condition of GMP of all manufacturing sites. The quality system in which the manufacturer is inserted. Evaluation of the packing material or the raw material against the manufacturer requirements, textbooks or other requirements. Who provides the Certificate of Analysis (C of A) for the raw material. Note that it is unacceptable that the results of manufacturer C of A are transcribed from the original C of A to the letter from the supplier. Acceptability of the samples provided with reference to the chemical, microbiological and physical attributes. If the manufacturing site has been audited and by whom. If the manufacturer has been contacted in previous occasions or other materials are supplied by this manufacturer. Any other material is being produced at the manufacturing site. Information about how the material is produced and what impurities may be present as a result of the production process. Relevant information about the testing methods used by the manufacturer. The real supplier of the tests that are documented in the Certificate of Analysis. Information about pesticides, process validation, and validation information of the analytical method. Confirmation that the manufacturer represents a single and specific source of the material. The manufacturer must collect and mix materials from various sources, which makes difficult the reduction of tests in this supplier qualification. Attributes of stability of raw materials and requirements for transportation of the material.

6 4. Acquisition of relevant information about the supply chain of packaging material and raw materials Each step in the supply chain may have potential impact on the quality of the packaging material or raw material. The identification of all interactions with the material between the output of the manufacturer and the final delivery of the finished product may be useful. Location of Manufacturer. Location of Supplier For herbal materials, location of harvest, harvest time, herbs identification and methods of preparation (extraction, for example). If the provider stores the material and the location and types of other materials are stored next to the material of interest. If the supplier fragments the material and the environment and the manner in which this activity is conducted. If the supplier has a technical agreement with the manufacturer and the contents of this agreement (for example, changes of material, such as method of manufacturing or supplying of material). The number of middlemen and the control of the transport chain from the manufacturer to the manufacturer of the finished product. Any material with requirements for specific storage such as refrigeration or humidity control. The time required for raw materials usually is received at the site. 5. Supplier approval of packaging material or raw material Information obtained in previous steps are evaluated by the Quality Unit and, if acceptable, the supplier may be approved When the raw material is supplied by a manufacturer that has a license and GMP certification issued by a health authority, then no other qualification is required from the manufacturer. The license or certification must cover the manufacturing of the specific material or the bulk and a GMP agreement must be established. To other suppliers a formal agreement that covers all relevant issues is recommended. how the supplier's approval system will rank the various levels or status of its approved suppliers and qualified. 6. Authorization of the specification of packaging material or raw material. The specification must be based on a paper when available and any relevant information provided by the manufacturer. If the material is supplied by a distributor / supplier, and if this is the case, the manufacturer has identified and documented the material specification. If C of A clearly provides documents of the test methods used, the acceptable specification limits and the results obtained by the manufacturer. If all tests performed by the manufacturer are compendial tests. If any non-compendial tests are properly validated. 7. Packing material or raw material purchased and used to manufacture the finished product In this phase, each delivery of a specific number of batches of raw materials would be approved by the Quality Unit after the total sample and all tests with satisfactory results.

7 Typically, three batches of raw material would be subjected to a complete sampling and testing, however, specific requirements of raw material may change this number. The standards that exist for the raw material. Number of deliveries received per year. Number of different batches received per year. The history of the Supplier. History of the raw material manufacturer. 8. Analysis and Data Trends All relevant data can be revised in accordance with the acceptance criteria defined. The information can be used to support a justification for a reduced sampling. The review of the physical condition of each lot of raw material. Review of the documentation that accompanied each batch of raw material. If all the results meet the specification of requirements. Review of any results out of specification or out of trend and any investigation followed by the conclusions. A statistical comparison of the results of tests performed in their own laboratory against the results issued by the manufacturer of the raw material when appropriate. 9. Qualification of the supplier of packaging material or raw material Assessment of all information collected from the supplier of packaging material or raw material. and it can be achieved through documentation review, questionnaires and audits. The minimum information to be evaluated by the Quality Unit must include a supplier qualification questionnaire completed and, if possible, an on-site audit of the manufacturing of raw materials. The information can be used to support the qualification of the supplier. Assessment of the supplier qualification questionnaire. The assessment of any other relevant information. Evaluation by an on-site audit of manufacturing and supplier, as required. If appropriate measures are in place to ensure the origin of the raw material in order to protect it against counterfeit materials. 10. Periodic Review As part of the qualification process, a program of periodic review must be established. This program should include a mechanism to remove the qualification status of a supplier of packaging material or raw material and should prevent the use of limited sampling and reduced tests until the critical issues identified are satisfactorily resolved. The Quality System of the manufacturer of raw material. The Quality System of the supplier.. The quality of batches of raw material received. Documentation reviews. Analysis of trends. Information obtained through questionnaires and audits of suppliers. This evaluation must be conducted by authorized personnel from the Quality Unit

8 Considerations About The Criticality Of Suppliers The buyer or contractor must target their suppliers as critical and noncritical" taking actions of qualification or disqualification, depending on the scores achieved. Depending on the results of evaluations of the supplier, they can still be considered "qualified", or negotiate a period to qualify or even, depending on the number of nonconformities and the possible impacts that these are causing or may cause in the buyer's processes, in the raw materials, finished products and even in the final customers (brokers, traders, users, consumers) they can be "Disqualified". In spite of the criteria established in this program, each company has their independence to set their own criteria for accreditation, to select and evaluate suppliers. It can set their criteria for criticality, taking into account, among others, aspects of health and safety, logistics, fulfilment of agreed schedules, productivity, financial aspects, if it is the exclusive supplier, existing certificates, index of the nonconformities in the receiving and process, prices, types of freight, warranties, location, among other factors. Bibliography - ANVISA Resolução da Diretoria Colegiada RDC 17 Regulamento Técnico de Boas Práticas de Fabricação de Medicamentos 16 de abril de ICH Harmonized Tripartite Guideline Q9 Quality Management. - ICH Harmonized Tripartite Guideline Q10 Pharmaceutical Quality System. - PIC/S Guide to Good Manufacturing Practice for Medicinal Products, January 2009 including Annexes. - Sampling and Testing of Complementary Medicines. May Technical Working Group on Complementary Medicines. - Technical Guidance on the interpretation of Manufacturing Standards. Supplier Qualification: Technical Working Groups (TWG) on Non-Sterile Medicines & Complementary Medicines. V1.0 September Kesia Pires Project Manager of Telstar Life Science value service - Brasil Conclusion The process of qualifying suppliers can be developed in different ways, being the example above only one of them. In this article, it was also demonstrated the possibility to use tools for prioritization of audits of suppliers in order to establish a "Supplier Qualification Program" that can be coherent and attainable.