QMS-115 Criteria for Sourcing of Raw Materials, Packaging Components & Imported Finished Goods

Document Owner

Supply Chain Manager

Affected Parties

Colleagues working in sourcing of raw materials, packaging components, bulk actives and imported finished goods in Technical Service, Supply Chain, Procurement and Laboratory Departments.

Purpose

The purpose of this SOP is to describe the process for approval of an external vendor/manufacturer supplying products into a manufacturing site.  It covers active raw materials (including bulk products for subsidiaries and contract manufacturers), excipients, critical packaging components in contact with product and imported finished goods. The SOP also references affiliated documentation detailing the scope of active materials used and the approved manufacturers of these materials.

Scope

Definition

Related Documents

EHS Statement

There are no EHS issues with documentation.

Procedure

1. Aim

The aim is of this SOP to define a manufacturer and vendor; detail selection criteria and selection procedures; provide details for the assessment of manufacturers and processes for approval of the manufacturers.

Active materials can only be obtained from approved manufacturers and in accordance with the registered details of the products with regulatory agencies.

Excipients and critical packaging materials are obtained from manufacturers capable of supplying material of the required grade and complying with the specified standard and/or  specifications.

Bulk products for packing and imported finished goods from contract manufacturers. These products are obtained from the contract manufacturers in accordance with the registered details of the regulatory authorities.

Mention is also made for approved vendors in ISO 9000 and the relevant Code of GMP.

2. Definitions

2.1. Vendor Actives, Excipients and Critical Packaging Components

A vendor is a company from whom we directly obtain the material.  (The ‘vendor’ may also be called the ‘Agent’, ‘Distributor’, or ‘Supplier’.)  The vendor may also be the manufacturer and may be local or overseas based.  The decision as to which vendor is used to supply the material is one of consultation with Supply Chain, Technical, and Laboratory departments.  The non-manufacturing vendor can only purchase material from the approved manufacturer as directed by site.

2.2.  Manufacturer

A manufacturer is the company that synthesizes or produces the material.  The manufacturer is normally responsible for all aspects of manufacture and quality control of the material.  Technical support is often provided with respect to product knowledge, stability data, impurity profile of the material and technical expertise relating to the material.  In the case of active manufacturers the manufacturer is responsible for the provision and maintenance of a Product Master File.

2.2.1. Approved Manufacturer Active materials

A manufacturer is designated as approved under the following conditions:

a) Via the legislation of regulatory authority.

b) Following submission of data as part of a product registration process.

The manufacturer may be local or overseas based.  The approval of a manufacturer includes compliance with GMP as authorized by a recognized regulatory authority.

2.2.2. Approved Manufacturer Excipient Materials

There is no requirement to specify the manufacturer of an excipient material for the registration of a product.  It is mandatory that the material supplied must comply with the grade and material specification registered as part of the registration process.  The specification to which the material must comply may have been registered under the following conditions:

a) Via the legislation of local regulatory authority.

b) Following submission of data as part of a product registration process.

The manufacturer may be local or overseas based.  It is preferred that a manufacturer of excipient materials be recognized as complying with GMP principles, yet this is not a legal requirement for these type of manufacturers.

2.3. Approved Manufacturer Critical Packaging Components

In most instances the manufacturers of critical packaging components are identified as part of the registration process, yet this is dependent upon the class of material.  This may be via the legislation of local regulatory authority or submission of actual data for the more recent registrations.

The manufacturer may be local or overseas based.  It is preferred that a manufacturer of critical packaging components be recognized as complying with GMP principles, yet this is not a legal requirement for these type of manufacturers.

2.4. Approved Manufacturer Bulk Products and Imported Finished Goods

A manufacturer is designated as approved under the following conditions:

a) Via the legislation of local regulatory authority.

b) Following submission of data as part of a product registration process.

The approval of a manufacturer includes compliance with GMP as authorized by a recognized regulatory authority.

3. Selection Procedure

3.1. General Requirements Vendor

Vendors are selected using the following parameters:

a) Ability to consistently supply material to the specification (laboratory records).

b) Ability to deliver the required material in the quantities ordered in the required timeframe (Procurement records).

c) Previous experience with the vendor (raw material records, laboratory records, reject material/component forms).

3.2. General Requirements Manufacturer

The selection procedure for a manufacturer of a raw material is dependent upon the classification of the material, i.e. active, excipient or critical packaging component, however there are a number of parameters, which are common:

3.2.1. Ability to consistently comply with the agreed material specification requirements.

3.2.2. Previous experience with the manufacturer.

3.2.3. Perceived reputation of the manufacturer within the industry and with regulatory authorities (communication, newsletters).

3.2.4. Level of technical support where required, which encompasses availability of product Master file, related substances (where applicable) and access to Head Office Technical/Research departments.  Pilot production runs with the material demonstrating satisfactory conformance, where required.

3.2.5. Corporate Supply Chain recommendation/requirement based on quality, audits and commercial evaluation.

3.2.6. The ability to demonstrate continuous improvement in products and processes.

3.3.  Active Material

In addition to the general requirements described above, material supplied from a particular manufacturer must undergo extensive evaluation both as the bulk raw material and with studies of product formulated using the material.  The studies encompass chemical and physico-chemical evaluations of finished products, production processing studies (where applicable) and stability trials covering long-term studies under various conditions and accelerated studies under stressed conditions.

A multi-stage approach is employed in selecting an active material as detailed below.

3.3.1. Stage 1

A sample of the active is analyzed using the test methods specified in the current standard methods (i.e. BP/USP) provided by the manufacturer and any additional  requirements where applicable.  Compliance with the requisite specifications is mandatory prior to continuation of the evaluation to the next stage of the process.  Particular attention is given to the purity and content of degradation products in the material.

In the case where a manufacturer is being evaluated to replace a current manufacturer or to augment the supply situation by having dual manufacturers then the new material is also analyzed against the current material with emphasis given to the purity profile between the two materials.  The test procedures used are those for the current material.  It is a prerequisite that the new material be of equal quality to that of the current material.  In particular, the impurity profile of the new material must be the same or preferably purer than the current material.

3.3.2. Stage 2 (where applicable)

Development formulations filled into the proposed container systems are prepared and subjected to conditions to simulate a rapid stability study to ascertain the appropriateness of the material.  The conditions to be laid down for the rapid stability trials are determined by a project team and are dependent upon the type of formulation, chemistry of the active, physico-chemical properties of the container and container material.

The stability profile is reviewed in accordance with pharmacopoeial and/or  other requirements.  The stability studies may be augmented by additional degradation studies where the raw material and formulations are subjected to oxidation, heat, light and acid/base conditions.  Any degradation products arising from the study are examined and the implication of these evaluated.

3.3.3. Stage 3 (where applicable)

A minimum of two batches of each formulation are prepared, filled into the proposed container using production equipment and subjected to routine stability studies.  The batch size of these development batches must be greater than 10% of the expected production batch.  Documentation for the manufacture and filling of the stability trial batches are written and authorized by the Technical Service Department and the Laboratory

Both accelerated and real time studies are carried out.  This process is designed to simulate the final production process in order to determine the final shelf life of the product as it would be supplied to the market.  The storage conditions for these trials are determined as described under Stage 2.  Where rapid stability studies had been performed the results from these studies are also taken into consideration when setting the storage conditions for the studies under Stage 3.

3.3.4. Stage 4

At the completion of the stability studies, technical documentation is prepared for the registration file.  This documentation includes, stability reports, expert reports, all specifications, formulations, methods of manufacture and component details.  The documentation is prepared in accordance with SOP QMS-030.

3.4. Excipient Materials

The choice of manufacturer is primarily dependent upon the capability of the manufacturer to provide material, which complies with the specified grade and registered specification.  The requirements under 3.2 must also be fulfilled.

Contact with excipient material vendors/manufacturers is limited.  Since the material quality is governed in the majority of cases to pharmacopoeial grade materials, the choice of vendors is limited to those companies who can comply with the stringent material specifications needed for pharmaceutical use.  Appropriate audits of the company are to be carried out in order to evaluation of the material.

3.4.1. A Pre-Procurement sample of the material is analyzed using the test methods specified in the current pharmacopoeial monograph and any additional  requirements where applicable.

3.4.2. Where necessary, production trials may also be carried out to assess any influences on the process.  The extent of the trials to be run is determined by a project team.  This information may be disseminated either via memo, trial protocol, master file and/or batch documentation.  Where master file documents are required, these are prepared in accordance with SOP QMS-030.

3.4.3. Where a dual or replacement manufacturer is sought the new material is also analyzed against the current material with emphasis given to the purity profile between the two materials.  The test procedures used are those for the current material.  It is a prerequisite that the new material be of equivalent quality to that of the current material.

3.5. Critical Packaging Components

3.5.1. In addition to the general requirements described above, the material is evaluated with respect to its chemical and physico-chemical parameters against compendia or other specifications, and where required undergo compatibility studies with the other components of the container system and/or stability studies with product filled into that container system.  In addition machine or processing trials are necessary.  Stability trials of product filled into the container system may entail long-term studies under various conditions and accelerated studies under stressed conditions.

3.5.2. The type of stability trials and processing trials to be performed is determined by a project team.  The extent of the trials is dependent upon the physico-chemical properties of the component, the component material, the type of products utilizing the component, machine capability, etc.

3.5.3. The information regarding the trials may be disseminated either via memo, trial protocol, Master file and/or batch documentation.  Where master file or batch documents are required these are prepared in accordance with SOP QMS-030.

3.5.4. The selection process and studies are similar to that described for Stages 1 to 3 under point 3.3 above.  The need to prepare a registration file as per Stage 4 is assessed dependent upon the registered details and country specific regulatory requirements.

3.6. Bulk Products and Imported Finished Goods

3.6.1. The choice of manufacturer is governed by agreement with the Corporate Supply Chain strategy.  The sourcing decision reflects the capability of the company or contract site to produce designated product types and provide technical support.

3.6.2. Technical documentation may be provided directly from Quality Management and/or as part of the certified Product Details from the regulatory authority.

4. Manufacturer Assessment

4.1. Following the initial selection process a technical assessment, according to the material specification and performance in production, is performed on the first five full production deliveries.

4.2. Subsequent deliveries are continually monitored through the Key Production Indicators (KPI) in the Service Level Agreement which include compliance to specification, delivery in full on time, adherence to packaging requirements and products received free of damage. The quality of the materials is also monitored as part of the post production stability surveillance program of finished products which utilise these materials.  Vendors/manufacturers are evaluated based upon the following criteria:

4.3. An annual vendor review is performed and documented by the procurement team using quarterly Service Level Agreements and KPIs, review data and additional information provided from QC test results, stability analyses from post production stability monitoring, production records, and Deviation Reports

4.4. If an adverse trend is detected by routine testing of the materials then the Laboratory Manager, in conjunction with the Procurement Manager, will review, discuss and take appropriate action.

4.5. Audits of the Manufacturing site for active materials and finished products are mandatory and are carried out by accredited Auditors. Audits of manufacturers producing excipients and critical packaging components, while not mandatory, are recommended in order to verify that the company operates under acceptable manufacturing procedures and systems.

5. Documentation Process for Approved Manufacturers

5.1. General

The status of manufacturers (that is whether they are approved, non-approved or discontinued) is disseminated to the QA, Procurement and Technical departments via memo by Technical Service Manager. This initiates the following steps:

5.1.1. The preparation of a material specification or modification of an existing specification in accordance with SOP QMS-030. The Technical Service Associate prepares specifications for critical packaging materials.

5.1.2. The Procurement Department negotiates and formalizes a supply and service level agreement which is singed by both parties.

5.1.3. This SOP need to be updated accordingly.

5.2. Approved Manufacturers Raw Materials

The range of all raw materials (including actives) and associated manufacturers/ vendors are listed in details in Technical Service documentation area.

5.3. Approved Manufacturers Imported Products

This is maintained in Product Register in Technical Service documentation area.

Summary of Changes