Easy Learning ICH Q7-Part 1

The series is to comprehend Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients-ICH Q7

Total Section/Chapters are 20 where 1st and 20th Chapters are Introduction and Glossary

The GMP Systems (General Requirement)

Every pharmaceutical manufacturer is responsible for establishing a GMP system in his manufacturing industry. In order to maintain an established framework of GMP system in theThe most essential requirements for maintaining good manufacturing practices in pharmaceutical industries is to have a strong system for

• Personnel
• Premises 
• Equipment
• Standard operating procedures 

Data Integrity-PART A

The data integrity has turned into an intense issue which is bringing association a terrible name during regulatory inspection. The administrative body trusts that the organisation where the information is precise, reliable and accurate and follow the regulatory guidelines and SOPs are working legitimately.

Flow diagram to handle Deviation

DEVIATION HANDLING AND MANAGEMENT

ALSO READ

Deviation Control And Management

Difference between Rework and Reprocess

Rework and reprocess are very confusing terms. There has always been an uncertainty which procedure is to be followed. Below is an effort to define both in simple terminology

To understand rework and reprocess the first thing is to make it clear that the material which is supposed to be reworked or reprocessed are always the non-conforming products. It means while assessing the disposition of the nonconforming products it will be analysed whether the product shall be reworked or reprocessed.

Rework and reprocess are both not routinely done.

Rework will be done when the material or drug is not having the desired standards, as a result an extra work is done to bring it back to the set standard. This effort of extra work is different from the established validated manufacturing procedure. This is not always necessary that rework is applicable to each and every industry. Nevertheless every industry must have the procedure for rework and at least the middle management and higher are aware of the concept of "Rework".

On the other hand "reprocess is the repetition of the same predefined process."

Therefore, in order to decide whether the SOP of rework or reprocess is to be followed, the first thing which shall come to mind is that the product is a non conforming product. This shall be brought to the notice of higher management. The NCR committee shall decide the disposition of the material.

During decision of the disposition the committee may decide that the material may again follow the same validated procedure or a procedure which is different from the established procedure.

If the same validated procedure is followed than the material is considered to be reprocessed on the other hand if different procedure is followed than the material is said to be reworked.

AUTHOR: ANSHU YADAV

anshuyadav.icgian@gmail.com

quallpharmaconsultancy@gmail.com

How to plan a Self inspection or Internal Audit

Internal audits are important within the manufacturing facility to recheck the existing system and to give assurance that an organisation's internal controls are .operating effectively.

HOW TO DETERMINE QUALITY IMPACT ON THE PRODUCT

While determining the quality impact of any event identified in the manufacturing of an API, the below aspect shall be studied but not limited to

1. Does it affect the final application or use by the customer?
2. Does it affect the storage condition of the product?
3. Does it affect the packing of the product?
4. Does it affect the transportation of the product?
5. Does it affect the Human safety?
6. Does it affect the Critical control point?
7. Does it affect the stability of the product?

If yes to any of the above questionnaire than there is quality impact on the API product,
If No to all the above questionnaire than there is no quality impact on the API product.

In case there is a quality impact the disposition of the product is to be decided.

Readers may contact the author at anshuyadav.icgian@gmail.com.

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Quality Risk Management

AUTHOR: ANSHU YADAV

quallpharmaconsultancy@gmail.com

anshuyadav.icgian@gmail.com

DEVIATION CONTROL AND MANAGEMENT

The aim of the document is to contribute to the understanding of a quality risk management approach in the handling of deviations from practical perspective as per WHO expectations on the matter.

The document is in line with documents like ICH Q10 Pharmacuetical Quality System, ICH Q9 Quality Risk Management like WHO, FDA and EU requirement.

Procedure:

• Deviation: Any departure from an approved instruction or established standards [Glossary of ICH Q7 –Good manufacturing guide for active pharmaceutical ingredients]
• Event Categorisation
• Identification of an Event- Anything that happens or takes place, especially important for notification.
• The decision tree described in the Flow diagram Diagram  is a simplified risk assessment that answer the following questions when an event is encountered:
• Effect on the product attribute
• Effect on manufacturing operational parameter.
• Effect on the Product quality.
• Contradict or omit specified requirement.
• Effect on the cGMP
• The specified requirements mentioned in 1.2.2.4 may be from any of the following:
• Standard Operating procedures that may cover any subject.
• Inspection and testing protocols.
• Customer specified requirements.
• Regulatory requirement.
• Technical instruction.
• Specified parameters written in forms and formats, log books and registers.
• HACCP plan.
• Drawing
• Specifications
• Incidents
• If the answer is NO for questions 1.2.2.1 and 1.2.2.5 above, the event may be considered an Incident.
• On the contrary, if any of the answer for questions 1.2.2.1 and 1.2.2.5 is YES the event shall follow the path towards a deviation category.
• Deviation
• A deviation is a situation that has occurred either in a planned or unplanned manner. It may be on a product or a process.
• Planned Deviation: Any deviation from a documented procedure or specified requirement adopted deliberately as a temporary measures.
• Unplanned Deviation: Any deviation occurred in an unintentional manner due to system failure, equipment breakdown, human error or any unforeseen circumstances.
• Minor Deviation - When the deviation does not affect any quality attributes, an operational or manufacturing parameters, or an equipment or instrument associated with the process, it is considered as Minor deviation.
• Major Deviation- When the deviation affects the quality attributes, an operational or manufacturing parameters, or an equipment or instrument associated with the process, of which the impact to personnel/environment is unlikely, the deviation is categorise as Major deviation.
• Critical Deviation- When the deviation affects the quality attributes, an operational or manufacturing parameters, or an equipment or instrument associated with the process, of which the impact to personnel/environment is highly probable is categorise as critical deviation
• Event Handling
• Identification of an Event- Anything that happens or takes place, especially important for notification.
• Whenever such event comes to notice use format no. F01 (Mail to anshuyadav.icgian@gmail.com if format is required) to identify whether it is an incident or Deviation and to classify it as planned or unplanned deviation.
• If it is an unplanned deviation than use format No F02 (Mail to anshuyadav.icgian@gmail.com if format is required)  to classify it as minor, major or critical.
• If it is a planned deviation than use format No F03 (Change control format)
• If it is and minor deviation/ incident than use format No F04(Mail to anshuyadav.icgian@gmail.com if format is required)
• Steps to handing Minor Deviation/Incidentt:
• Description of an Event
• Correction
• Efficacy and Conclusion
• Recording
•  Monitoring

NOTE:

Minor deviation shall be reviewed by Manager QA, recommended by department HOD and approved by Head QA

• Handling major deviations/critical deviations
•  Description of an event
•  Correction
•  Efficacy and Conclusion
• Root cause investigation 
• Investigation shall be done by using  5 why technique etc.
• An investigation report shall be generated which shall have the below contents but not limited to :
• Reason for investigation(what event or finding prompted investigation, how and when happened)
• Describe what happened(when and where)
•  Identify other batches/lots affected
•  Identify root cause
• Quality Impact
• The Quality impact shall be assessed by Quality Risk Management SOP. If there is a quality impact the product is considered as non-confirming product.
• Recommendation from department head, approval from Head QA and authorization by Director TQM.
•  Validation impact/supporting document.
• Assessment of validation impact (Shall be done by Departmental Head/Head QA and Director TQM)
• CAPA
• Efficacy of corrective action
• Conclusion

  Note:      Major/Critical deviation shall be reviewed by Manager QA, recommended by department HOD and approved by Head QA and authorized by Director TQM.

•  Handling of planned deviation
• Description of an event
•  Justification for requirement of planned deviation
•  Quality Impact
• The Quality impact shall be assessed by Quality Risk Management SOP. If there is a quality impact the product is considered as non-confirming product 
•  Validation impact/supporting document.
•  Assessment of validation impact.
•  CAPA
•  Efficacy of corrective action
• Conclusion
• Recording
• Monitoring

Note:Planned deviation shall be reviewed by Manager QA, recommended by department HOD and approved by Head QA and authorised by Director TQM.

• QA shall retain the records irrespective of the approved / reject status of the deviation report and a photocopy of the same shall be filed with the subjected batch manufacturing / packing record/analytical reports.
• Wherever a deviation could affect multiple batches, e.g. due to equipment or facility failure or material or process deviation report, a photocopy of the same shall be filed with the subjected batch manufacturing / packing record / analytical report.
• If it is found that the deviation occurred on account of a faulty procedure or process, action shall be taken to amend the concerned document under company’s document change system for necessary amendments to the affected documents.
• QA personnel shall maintain the deviation log, department wise, and year wise as per the Deviation Control Log (Mail to anshuyadav.icgian@gmail.com).
• Deviation/INCIDENT control numbering system (For details mail to anshuyadav.icgian@gmail.com)

If there are any query, questions or suggestion related to the article, please mail back to anshuyadav.icgian@gmail.com.

AUTHOR: ANSHU YADAV

anshuyadav.icgian@gmail.com 

         

Analysis of warning letter issued by US-FDA

An inspection took place in one of the food manufacturing facility by investigator of US-FDA. During that inspection significant violations were observed against 21 CFR part 110 regulation which causes the food product that the company manufactures to be adulterated within the meaning of Section 402 (a) (4) of Federal Food. Drug, and cosmetic act [ 21 U.S.C. 342 (a) (4)].

21 CFR part 110 here refers to current good manufacturing practices in manufacturing, packing or holding human food. 

and Section 402 (a) (4) of Federal Food. Drug, and cosmetic act [ 21 U.S.C. 342 (a) (4) says that
If the product has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health;

Below are some of the observation which each food and pharma company shall review at theier manufacturing premises and understand how it is linked with code of federal regulations.

Observation 1- The firm failed to take effective measures so that the pest could be excluded from the processing area and to protect against the contamination of food on the premises by pests.These requirements are mentioned in 21 CFR 110.35(c) and 21 CFR 110.20 (b)(7)

21 CFR 110.35(c)
Where 
Title 21-Food and Drugs
CFR refers to Code of federal regulation
PART 110- CURRENT GOOD MANUFACTURING IN MANUFACTURING, PACKING OR HOLDING HUMAN FOOD.
Sec.110.35 Sanitary Operations

21 CFR 110.35(c) Pest Control : No pests shall be allowed in any area of the food plant, Guard or guide dogs may be allowed in some areas of a plant if the presence of the dogs is unlikely to result in contamination of food, food contact surfaces, or food packaging materials. Effective measures shall be taken to exclude pests from the processing areas and to protect against the contamination of food on the premises by pests. The use of insecticide or rodenticide is permitted only under precautions and restrictions that will protect against the contamination of food, food contact surfaces, and food packaging materials.

21 CFR 110.20 (b)(7) Provide, where necessary, adequate screening or other protection against pests.

Observation 2-Failure to conduct cleaning and sanitizing operations for utensils and equipment in a manner that protects against contamination of food and food contact surfaces, as per 21 CFR 110.35(a) and 21 CFR 110.3(o)

21 CFR 110.35 (a) GENERAL MAINTENANCE

Building, fixtures and other physical facilities of the plant shall be maintained in a sanitary condition and shall be kept in repair sufficient to prevent food from becoming adulterated. Cleaning and sanitizing of utensils and equipment shall be conducted in a manner that protects against contamination of food, food contact surfaces, or food-packaging material.

21 CFR 110.3(o)
Sanitize means to adequately treat food contact surfaces by a process that is effective in destroying vegetative cells of microorganism of public health significance, and in substantially reducing numbers of other undesirable microorganism, but without adversely affecting the product or its safety for the consumer.

Observation 3 

Lack of effective hand cleaning and sanitizing preparations, as per 21 CFR 110.37(e).

As per 21 CFR 110.37 (e) Hand washing facilities: Hand washing facilities shall be adequately and convenient and be furnished with running water at a suitable temperature. Compliance with this requirement may be accomplished by providing:

1) Hand washing and, where appropriate, hand sanitizing facilities at each location in the plant where good sanitary practices require employees to wash and/or sanitize their hands.

2) Effective hand cleaning and sanitizing preparations

3) Sanitary towel services or suitable drying devices.

4) Device or fixtures, such as water control valves, so designed and constructed to protect against recontamination of clean, sanitized hands.

5) Readily understandable sign directing employees handling unprotected food, unprotected food-packaging materials, of food contact surfaces to wash and, where appropriate, sanitize their hands before they start work, after each absence from post of duty, and when their hands may become soiled or contaminated. These sign may be posted in the processing room(s) and in all other areas where employees may handle such food, material, or surfaces.

6) Refuse receptacles that are constructed and maintained in a manner that protects against contamination of foods.

7) Rubbish and offal disposal  shall be so conveyed, stored and disposed of as to minimize the development of odor, minimise the potential for the waste becoming an attractant and harborage or breeding place for pests, and protecting against contamination of food, food contact surfaces, water supplies and ground surfaces.

If there are any query, question related to the article, readers are requested to mail their query at anshuyadav.icgian@gmail.com.

Author : ANSHU YADAV

anshuyadav.icgian@gmail.com.

DEVIATIONS

Deviation can be defined as departure from an approved instruction or established standard.

Such deviation may adversely affect the desired quality of the pharmaceutical product. Such deviation must be avoided, but if required than must be justified and explained if there is any quality impact on the pharmaceutical product. The noted deviation must be properly authorised and recorded. The deviation are defined in ICH Q7 as well as M schedule.

ICH Q7 states that

1. Any  deviation from the established procedure should be documented and explained. Critical deviation should be investigated and the investigation and its conclusion should be documented.
2. It is the responsibility of the quality units to ensure that critical deviations are reported, evaluated, completed and signed.
3. In product quality review, a review of all critical deviation or non conformance and related investigation must be recorded.
4. Deviation from the approved standards of calibration on critical instruments should be investigated if stored separately.
5. Written procedure should be established and followed for investigating critical deviations or the failure of a batch of intermediate or API to meet the specification. the investigation should extend to other batches that may have been associated with the specific failure or deviation.
6. All deviation reports should be reviewed as part of the batch record review before the batch is released.
7. Deviation in yield associated with critical process steps should be investigated to determine their impact or potential impact on the resulting quality of affected batches.
8. A validation report that cross reference the validation protocol should be prepared, summarising the result obtained, commenting on any deviation observed and drawing the appropriate conclusion including recommending changes to correct deficiency.

M schedule also talks about deviation but not in so much of details. As per M schedule :

1.  Comments or explanation for significant yield limit shall be given.
2.  There shall be notes on special problems including details with signed authorisation for any    deviation from the master formula. 

If there are any query, question related to the articleor requirement of deviation formats , readers are requested to mail there query at anshuyadav.icgian@gmail.com.