VAL-035 In-House Trial Procedure

1. Introduction

Trials are necessary to provide data for review of continuous improvement initiatives, submissions to regulatory authorities and for validation purposes. Trials need to be designed, executed, evaluated and documented in way that ensures there are no GMP breaches.

Communication with all stakeholders (including Engineering, Production QA personnel) is essential to explore the impact of the trial, to communicate the purpose of the trial, and to gain support and acceptance for the trial.

2. General Types of Trial

2.1. Different types of Trials include, but are not limited to:

Equipment trials/review

Used to evaluate whether a change to or a new piece of equipment is desirable.

Process trials, which may include:

Stability trials, (for example: Increasing the batch sizes for a product).

Change in Component trial, (for example: a Change in the leaflet size).

Production Method Trial, (for example: an additional process steps).

Process Improvement Trial

Qualification / Validation

3. Trial Stages

Trial Checklist Form (Form-340) can be used to facilitate the timely and effective preparation and execution of any trial.

3.1. Initiation

The initiator of the trial will:

3.1.1. Present the reason for the Trial to the appropriate Manager and list the Trial objectives.

3.1.2. Identify other stakeholders and assess the impact that the Trial will have on other departments including Production, Planning, Technical, Engineering, Regulatory, QA and/or Validation.

3.1.2.1.   Organise a Pre-Trial Meeting to collect and disseminate information and to establish the Trial acceptance criteria, if applicable.

3.1.2.2.   The number of product batches included in the trial.

3.1.2.3.   The size of the product batches included in the trial.

3.1.2.4.   If saleable product or not.

3.1.2.5.   Timeframes for completion.

Note: For saleable product the Protocol must be enclosed with the Final Batch documents and a DR (QMS-035) needs to be raised to hold the release of the batch/s until all trial documentation has been completed and approved.

3.2. Trial Preparation

The following are responsibilities of the Trial Coordinator or a delegate.

3.2.1. Ensuring a Trial Protocol/Conclusion is written, (see Section 5 for guidance) and approved by QA, Production, Technical and/or Validation Management as applicable.

3.2.2. Providing support to the area in which the trial is to occur.  This will include explaining the requirements for the trial documentation, processes and procedures.  It will also include establishing communication processes to ensure trial requirements are met across all shifts and changes in personnel.

3.2.3. Obtain Area Manager’s approval and agreement to adequately resource the trial in terms of personnel, equipment and time.

3.3. Trial Execution

It is the responsibility of the area in which the trial is to take place to resource the trial in terms of personnel and equipment availability.   The Area Manager, (or delegate) will ensure:

3.3.1. The Trial Coordinator (or delegate) has provided Pre-Trial training/communication for all personnel affected by the trial should the trial warrant this.

3.3.2. A nominated person on each area is assigned to assist in co-ordination of the trial and documentation completion and review.  This person must have appropriate process knowledge to carry out these functions.

3.3.3. A trial BPN is raised when making trial product that is not saleable product.

3.3.4. For non-saleable trials blank packaging material is used when possible.  If this is not feasible, approval must be gained from QA for the use of printed materials.

3.3.5. For non-saleable trials all components are identified as trial materials.

3.3.6. All trials, (whether saleable product or not) are manufactured to GMP standards.

3.3.7. All components used for saleable product are those that would be used for manufacture of a routine production batches, i.e. comply to the BOM.

3.3.8. ALL trial documentation is kept.  Documentation must be completed to GMP requirements and treated as per a routine batch unless the trial documents specifically instruct otherwise.

3.3.9. ALL Laboratory samples, waste, product, reconciliations, in-process testing must be taken/performed as per a routine batch unless the trial documents specifically instruct otherwise.

3.4. Trial Completion

Once the actual trial has been executed, the documentation and results must be collated, the trial reported on, the batch disposition established, (where applicable) and the documents affected by the trial updated.

3.4.1. The area Manager, (or delegate) must collect the trial documentation generated and perform a review, using the checklist provided with the protocol, to ensure all documentation is present and complete.

3.4.2. The Trial Coordinator, (or delegate) is responsible for:

3.4.2.1. Performing a review of the documentation and collecting any additional data required, (including Laboratory reports).

3.4.2.2. Processing the results.

3.4.2.3. Drawing up a trial conclusion with a clear outcome of the trial.

3.4.2.4. Organising for the destruction of any non-saleable trial material.

3.4.2.5. Communicating the trial outcome to all affected parties.

3.4.3. Alterations to documents/processes as a result of the trial are to be carried out using the Change Control system.

4. Trial Preparation Checklist

The following lists some of the most common considerations that should be discussed at the Pre-Trial meeting:

4.1. How much the cost involved?

4.2. Does this trial have any impact on the product registration?

4.3. Are all trial components available? If not, what is the lead-time required to order these? Will this interfere with supply of routine production components?

4.4. Is this the most cost efficient way of achieving the trial outcome?

4.5. Are MI (Manufacturing Instruction) sheets required / are MI sheet amendments required?

4.6. What testing is required?  Are test methods available for all required testing?

4.7. Does each department have the resources (equipment and personnel) to support the trial?

a) Production – Review trial Protocol to ensure it can be fully understood by ALL production staff and it complies with the process.  Review trial report and provide sufficient trained personnel to support the trial.

b) Technical Service– Provide sufficient resources to create manufacturing instruction update technical documents and stability cards as necessary.

c) Validation/Engineering/QA – Provide sufficient resources to write trial Protocols, execute and support trial protocols and write trial reports.

d) Logistics – schedule trials and order/allocate components.

e) QA – Review documents for GMP compliance.

f) Laboratories – test products within allowed timeframes, draw up test methods if required, release batches.

g) Warehouse – Pick components specific to the trial, dispose of reject material after the trial, and ship finished goods.

5. Protocol for Trials

All documentation and data generated during the trial is considered GMP documentation for retention and archiving purposes.  It must be retained in a manner that permits traceability and ensures that it is readily retrievable.

The protocol must describe how the trial activities are to be executed and define the acceptance criteria.  It must be approved by QA, issued in advance of the work and be version controlled.  Where deemed appropriate, the rational, justification, scope, and strategy should be documented.

Trial Protocols and documentation must be flexible and tailored to the proposed trial.  The following checklist will assist protocol and documentation preparation:

The protocol should include the following, as appropriate:

– Detailed objectives

– Process description

– List of products

– List of process, facilities, systems and equipment to use

– Summary of critical parameters and activities to evaluate

– Number and identity of runs / batches

– Release specification/s and list of analytical methods

– Acceptance criteria

– Proposed in-process controls

– List of forms that are required to be filled by production

– Additional testing to be carried out

– Sampling plan and testing procedures

– Methods for recording and evaluating results

– Functions and responsibilities

– Proposed timetable

– Checklists to include all important steps

– Log sheets for all data to be recorded.

– Checklist listing equipment settings prior to alteration and confirming these have been returned to original setting on completion of trial. Entries need to be confirmed by a second person.

6. Trial Conclusion

The Trial Conclusion includes, but is not limited to:

6.1. The summary of the raw data and evaluation of the work against the acceptance criteria.

6.2. A clear conclusion, stating whether the trial has been completed and if successful or not.

6.3. Any recommendations for future implementations. 

7. Flowchart – Execution of Trials

8. Summary of Changes