CAPA risk management

One of the most commonly quoted, accepted definitions of risk is that it is the probability of harm or hazard in an event. From this definition, it is clear that nearly every clinical action comes with a risk attached to it. CAPA stands for Corrective and Preventive Action.

The CAPA-risk management connection

The risk an event carries in it is likely to cause physical damage to a product, into whose creation some risk is inbuilt. Risk could also result in damage to either the humans who are part of the process or to the environment. Thus, in a healthcare organization, the CAPA-risk management aspects are extremely important and are interwoven.

The effect of risk is never uniform or predictable. Its extent depends on the assessment its stakeholders make of it. To arrive at the quantum or gravity of the damage caused by a risk, CAPA is needed. This gives some idea of the CAPA-risk management connection.

CAPA-risk management is inseparable

As we saw, CAPA goes into a process to mitigate risk. Since CAPA is an effective method of identifying, correcting and preventing the risk in a process; clinicians have to keep a few important CAPA-risk management factors in mind:

  1. Is the nature of the hazard old or new?
  2. Has the severity changed since the process began or not?
  3. What is the frequency of the occurrence of the risk that is to be analyzed?
  4. How to identify the causes of risk.

Reference:

http://www.mddionline.com/article/best-practices-managing-capa-system

http://www.google.co.in/url?sa=t&rct=j&q=capa%20and%20risk%20management&source=web&cd=2&cad=rja&ved=0CDAQFjAB&url=http%3A%2F%2Fwww.ehcca.com%2Fpresentations%2Fdevicecongress1%2Fcollazo_d.ppt&ei=1VOtUcW-LMjyrQe714CABg&usg=AFQjCNE2D2D4Kzwt9ifVxpnfam9RFetxUQ&bvm=bv.47244034,d.bmk

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CAPA and risk management

Risk has been often described as the probability of harm or hazard in an event. So, it is to be understood that in the healthcare industry, almost every clinical action has a risk inherent or attendant in it. CAPA, on the other hand, is about corrective and preventive action. From these definitions, we can draw a link between CAPA and risk management.

How are CAPA and risk management related to each other?

Risk can mean physical damage to a product arising out of a process that is necessary to perform. It could also mean damage caused to the humans involved in the process or to the environment. Assessing the risk factors is thus of paramount importance to a healthcare organization that is involved in some or another process.

An important element of risk is that its gravity on any single action is subjective. That is, different stakeholders place differing meanings and values for the risk levels in an action or outcome. It is to evaluate the extent of the damage caused by this risk that CAPA is evoked. Thus, CAPA and risk management share a cause-action relationship.

Why are CAPA and risk management built into each other?

CAPA is built into a process because it has to mitigate risk. It is one of the effective methods of identifying, correcting and preventing the risk got from a process. A few challenges have to be anticipated and overcome while implementing CAPA into the risk process.

  1. When to open a CAPA has to be identified clearly. This is difficult, because the effect and outcomes of processes keep changing over time;
  2. This is all the more difficult in combination products, because their process and result keep fluctuating through the process;
  3. When new procedures are introduced midway into the process, CAPA and risk management take a new form.

Factors to consider for CAPA and risk management

In implementing CAPA and risk management, clinicians have to keep a few important factors in mind:

  1. The nature of the hazard –whether old or new;
  2. What is the level of severity –has it changed since the process began or has it remained the same?
  3. The frequency of the occurrence of the risk has to be analyzed;
  4. It is necessary to identify the causes of risk;

This illustration provides some idea of how CAPA and risk management need to be built into each other:

 

Source: http://www.mddionline.com/sites/default/files/archive_images/mddi0606p52a.jpg

Reference:

http://www.mddionline.com/article/best-practices-managing-capa-system

http://www.google.co.in/url?sa=t&rct=j&q=capa%20and%20risk%20management&source=web&cd=2&cad=rja&ved=0CDAQFjAB&url=http%3A%2F%2Fwww.ehcca.com%2Fpresentations%2Fdevicecongress1%2Fcollazo_d.ppt&ei=1VOtUcW-LMjyrQe714CABg&usg=AFQjCNE2D2D4Kzwt9ifVxpnfam9RFetxUQ&bvm=bv.47244034,d.bmk

 

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Calibration and qualification in analytical laboratories

Calibration and qualification in analytical laboratories is needed because laboratory equipment should demonstrate suitability for the intended use. The way to do this is by calibrating and qualifying them. Calibration and qualification in analytical laboratories are also necessary because they are subject to FDA inspections.

Laboratory equipment is high risk systems

Calibration and qualification in analytical laboratories are necessary also because laboratory equipment is high risk systems in that they impact product quality greatly. Because of this categorization, equipment calibration and qualification is a frequently cited deviation in FDA inspectional observations. They are also targets of warning letters. To avoid all these scenarios, calibration and qualification in analytical laboratories is called for, although it is possible that many times, companies are not sure on exactly which of their equipment they need to calibrate, qualify, test and document.

Important factors

Three important factors impact the reliability of analytical data generated from chemical and physical analyses critically:

  • How much validity the analytical methods used have;
  • The extent to which the instruments used for the experiments are reliable;
  • How well and how appropriately the analysts undertaking the calibration and training are trained

What does the FDA say?

The FDA’s c-GMP requirements (CFR – Code of Federal Regulations, Subpart I: Laboratory Controls, S211.160 (b) (4)) has this to say about the scope of calibration and qualification in analytical laboratories:

“The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.”

References:

http://www.cvg.ca/images/Qualification.pdf

http://www.labcompliance.com/seminars/audio/226/default.aspx

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Batch manufacturing record in pharmaceutical industry

A batch manufacturing record in pharmaceutical industry is information relating to the product and batch. It is a document that is intended to give a full and authoritative record of the manufacturing history of each batch of every product. The FDA defines a batch thus: “A specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture”.

System of checkpoints

In the light of this definition, batch manufacturing record in pharmaceutical industry has to be understood as one that is basically based on the master formula record. It is created, checked, ratified and sanctioned by the designated, competent technical person/s that is responsible for the organization’s production and quality control.

In order to avoid wrongful reproduction, batch manufacturing record in pharmaceutical industry involves use of methods such as photo reproduction.

What should go into it?

A typical batch manufacturing record in pharmaceutical industry ideally consists of these details:

  • The product name
  • Its batch number
  • Date on which significant intermediate stage were commenced and completed
  • The name of  the person who is responsible for each stage of production
  • Initials of both operators who carried out significant processes and the persons who checked these
  • Details such as the quantity, batch number, quality control report number of each ingredient actually weighed, along with the amount of any recovered material that may have been added
  • Details of in-process controls, their results and signature of person who performed these
  • Whenever variation that exceeds expectation is observed, batch manufacturing record in pharmaceutical industry should make note of the theoretical yield and actual yield at every appropriate stage of production. These should be accompanied by an explanation
  • Details of authorization of any deviation, if any was made

References:

http://www.lifescienceleader.com/magazine/past-issues3/item/3502-is-the-reign-of-batch-processing-coming-to-an-end

http://malayinfo.blogspot.in/2012/07/issuance-of-batch-manufacturing-record.html

http://www.pharmatutor.org/articles/manufactuting-documentation-pharmaceutical-industry-development-implementation?page=0,1

 

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USP method transfer

USP method transfer underwent a change when the US Pharmacopoeia published the final version of its informational chapter 1224, which deals with the transfer of analytical procedures mentioned in the document entitled USP 35-NF 30. This became official in May 2012.

How is the new document different?

The US Pharmacopoeia had earlier issued the 1224 stimuli document in response to comments it received from users and professionals globally. The new version of chapter 1224, which is the general article, is different in one fundamental way in that it makes risk based assessment the criterion for the nature and scope of transfer activities. So, this new version of USP method transfer is different in one small, but very significant way.

What are the major elements of the new USP method transfer version?

The May 2012 USP method transfer recommends many new elements. Some of these are listed below:

  • The laboratories have to prepare a detailed analytical procedure with instructions that are sufficient and explicit enough to allow a trained analyst to perform it painlessly
  • All questions regarding the transfer process have to be clarified at a pre-transfer meeting between the transferring and the receiving units
  • The written analytical procedure and development validation reports have to be transferred to the receiving unit from the transferring unit
  • The transferring unit has to train staff of the receiving unit
  • A dry run of the procedure has to be conducted at the receiving unit
  • Issues that may need resolution have to be identified before the signing of the transfer protocol
  • All the required identification, calibration and qualification needed of respective analytical instruments have to be carried out
  • Compliance with relevant regulations of the laboratory systems of the two units has to be confirmed

What are the implications of failure to meet acceptance criteria?

According to the USP method transfer; failure of the sending or receiving fails to meet acceptance criteria qualifies as a serious, but not fatal error. It does not get classified under Out-of-Specification (OOS) result whose desired action is investigation into the root of the OOS. However, this requires discussion and justification of any deviation. Either of the laboratories –the sending or receiving –should investigate the reason for which the predicted acceptance criteria were not reached, and should take corrective measures. This process makes USP method transfer complete. The transfer can take place only when the acceptance criteria are met, the failure of which prevents the transfer from taking place.

Reference:

http://www.drugregulations.org/2012/05/new-usp-requirement-for-analytical.html

 

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USP 1058 analytical instrument qualification

USP 1058 analytical instrument qualification is about ensuring that an instrument is suitable for its intended use and application. While system suitability and method validation activities have specific guidelines and procedures; analytical instrument qualification is not so specific. There are conflicting opinions and viewpoints regarding USP 1058 analytical instrument qualification.

Though subjective, analytical instrument qualification is central

Analytical Instrument Qualification (AIQ) stands at the base of the components that go into data quality; the other three components being Analytical Method Validation, System Suitability Tests and Quality Control Check Samples. Why is this so? This is because a sound AIQ lies at the root of the ability of an instrument to meet its intended application. AIQ is not a standalone event in the analytical instrument qualification process. It consists of many related activities.

The four phases of AIQ

USP 1058 analytical instrument qualification requires activities to be grouped into four phases: Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).In brief, these are what these phases are:

Design Qualification

According to USP 1058 analytical instrument qualification; a DQ is the documented set of activities that lay out the functional and operational specifications of the instrument. It also mentions the criteria for selection of the vendor, based on the intended purpose of the instrument. The DQ can be performed by both the manufacturer and the user.

Installation Qualification

IQmay be described as the documented collection of activities that are necessary to establish that an instrument is a) delivered as designed and specified; b) it is properly installed in the selected environment, and c) this is done in an environment that is suitable for the instrument. Whether an instrument is new or was pre-owned, or exists on site but has not been previously qualified; IQ is required.

Operational Qualification

OQ testing follows IQ. It concerns the operational part of AIQ. It is the documented set of activities with which to demonstrate the ability of an instrument to function according to its operational specification in the selected environment.

Performance Qualification

PQ is the last stage of USP 1058 analytical instrument qualification. PQ is the documented collection of activities that is necessary to show that an instrument consistently performs according to the specifications defined by the user, and is appropriate for the intended use.

References:

http://www.drugfuture.com/Pharmacopoeia/USP32/pub/data/v32270/usp32nf27s0_c1058.html

 

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Sterilization

In lay terms, sterilization is understood in a number of ways. We have sterilization in economics, in family planning and in many other fields. When it comes to this term as used by the FDA; there is a specific purpose and definition. For the FDA, sterilization process controls are indispensable for validation.

Sterilization is part of inspections

Sterilization is essentially linked to inspectional objectives. The FDA states the following:  “for sterilization processes, the primary device specification is the desired Sterility Assurance Level (SAL). Other specifications may include sterilant residues and endotoxin levels.”

Important processes labs have to comply with

The FDA has a detailed set of processes that laboratories have to comply with. These are some of the more important ones:

  • The laboratory has to confirm that the sterilization process was validated after the validation study was reviewed
  • It has to review and verify the specific procedure or procedures for the said sterilization process, as well as for the methods that were used to control and monitor the process
  • If during the review of the Device History Records (which include process control and monitoring records, acceptance activity records, etc.) it is discovered that the sterilization process falls beyond the organization’s stated threshold for operating or performance parameters, the company has to do these:

–        It has to determine whether anynonconformance was taken care of in the prescribed manner; and

–        Once this is done, it has to review the equipment adjustment, calibration and maintenance

  • If the laboratory has a system in which the sterilization process is software controlled, it has to confirm that the software was validated
  • The company has to ensure that only appropriately qualified and trained personnel have to implement the sterilization process

Reference:

http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm170829.htm

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