Rule relating to orphan drugs in Japan

Orphan drugs are those that are developed purely to treat rare diseases. The nature of orphan drugs is a little piquant: on the one hand, rare diseases affect very few people, but these cannot be ignored. On the other hand, orphan drugs, since they are so few in number, are not taken up usually by profit-driven organizations because they offer very less scope for large-scale production and monetization.

Different countries such as the US and Japan, and blocs such as the European Union have their own unique rules regarding orphan drugs. Rules relating to orphan drugs in Japan too, have their unique and salient features.

A look at the uniqueness of rules relating to orphan drugs in Japan

Orphan drugs in Japan are governed by five incentives:

  • Subsidies
  • Consultation
  • Tax preferences
  • Priority review
  • Reexamination period review

Briefly, this is how each of these is carried out in practice:

Subsidies:The Japanese government has a fund of close to a billion yen that is used to subsidize orphan drug applicants. This grant, given through the National Institute of Biomedical Innovation (NIBIO), is aimed at helping manufacturers to ease the costs associated with development of orphan drugs in Japan.

Consultation:Under this system, the Japanese government offers priorities for manufacturers of orphan drugs in Japan. Called the Priority Consultation System; this process is offered in two ways:

One, when a sponsor of orphan drugs in Japan approaches the PMDA; the application is never rejected. Clinical data is discussed with each sponsor, at which all the aspects of orphan drugs in Japan are considered. Areas taken up for discussion include the number of patients, the intensity of the disease, the integrity and safety of the data, and so on.

Two, the fee category is also considerably lower for orphan drugs in Japan, with these manufacturers given about 25 percent discount. An application made for developing orphan drugs in Japan is put for consolation with a team of Technical Experts, who are selected from the Office of New Drug Review team, the Office of Cellular and Tissue-based Products Review team, and the Office of Medical Devices Review team. In addition, fee categories are drastically lower for orphan drugs in Japan when they are being developed by small companies or research institutes. These categories have a whopping 90 percent discount.

Tax incentive: Manufacturers involved in developing and manufacturing orphan drugs in Japan are given a 12 percent reduction as tax credits for expenses incurred during the NIBIO subsidy payment period.

Priority review:Manufacturers of orphan drugs in Japan are offered a priority review by the PMDA. While the median standard review time is one year for non-orphan drugs, that for orphan drugs in Japan is nine months.

Reexamination period review: The Reexamination period review for orphan drugs in Japan is also relaxed. It is fixed at eight years for orphan drugs in Japan, while this period is ten years for non-orphan drugs in Japan.

Read More: https://www.linkedin.com/pulse/rule-relating-orphan-drugs-japan-ronald-gardner

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

 

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539

 

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

 

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539

 

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

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539

 

Q7 guidelines

Q7 guidelines are those guidelines issued by the ICH (International Conference on Harmonization) in relation to Good Manufacturing Practices (GMP) for Active Pharmaceutical Ingredient (API).

Q7 guidelines are very comprehensive

More than 12 years after they were mooted in November 2000; Q7 guidelines continue to be the driving force for API GMP regulations around the world. These relate a large number of areas concerning API, some of which are:

  • Quality management, which covers principles, responsibilities of the Quality Unit(s), internal audits, product quality review and others;
  • Personnel, which takes into account personnel qualifications, hygiene and so on;
  • Qualifications of Consultants;
  • Building and facilities;
  • Process equipment;
  • Documentation and records;
  • Materials management;
  • Packaging and labeling, and so on.

Need for change

Despite the good intention and comprehensiveness of these guidelines; in October 2012, the ICH Working Group issued a concept paper on the working of these guidelines. The areas of concern were about harmonization as well as some ambiguities that had crept in into the working of this guideline.

The essence of the Working Group’s observations was summed up thus: “It has become apparent, based on the approval and implementation of ICH Q8, Q9, Q10, Q11 principles into GMP of APIs that certain individual implementation approaches are leading to non-harmonized interpretation and new expectations beyond the intention of ICH Q 7”.

Many areas need reform

According to the committee, many Q7 guidelines had issues that needed to be addressed and requiring review. These include supply chain control, outsource management, monitoring of impurity profiles, quality systems, the application of the guidance to biological medicines and biotechnology products, Q7’s relationship to the Q5D Guideline on the Quality of Biotechnological Products, and expectations for manufacturing done specifically for clinical trials.

More corrective action needed

It has said at the time of the release of this report that it will suggest changes to these Q7 guidelinesafter a new working group, formed for the purpose of assessing and recommending changes, will offer its advice on suggested issues.

References:

http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm129098.pdf

http://www.raps.org/focus-online/news/news-article-view/article/2520/ich-working-group-calls-for-revisions-to-q7-guideline.aspx

 

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539

 

Method transfer FDA

A method transfer is the process of qualifying a laboratory regarding its ability to carry out an analytical test procedure. For method transfer, FDA has some regulations that are simple on the face of it, but require many steps and precautions. Not being in compliance with these steps could invite investigation and corrective measures to ensure that validated method transfer is carried out.

For a lab to meet method transfer FDA has set; it has to ensure that some pre-method transfer steps are adhered to. These include:

  • Unambiguous and clear communication between the sending and receiving lab on all the aspects of method transfer
  • Nomination of ideally a single person or point of contact between the sending and receiving labs, a person who will coordinate on the details of the transfer
  • Complete and clear assessment of the method of transfer
  • Identification of the required method transfer
  • Evaluation of issues arising out of the context of the location, such as data collection systems, instruments and reagents and coagulants.

Documents to be sent by the sending laboratory

To meet method transfer for FDA requirements, the pre-approved transfer protocol of the sending laboratory will typically consist of the following documents:

  • General transfer process
  • Definition of responsibilities of both parties
  • Specifics of the acceptance data
  • A list of the methods
  • Categorization of the methods
  • A description of samples and materials
  • Description of batch and lot records
  • Definition of parameters and instrumentations

Materials to be sent by the sending laboratory

Talking about the materials to be provided by the sending laboratory, these are usually part of method transfer the FDA requires:

  • Method, which consists of system suitability parameters, rationale for chosen, parameters, step-by-step directions and safety considerations
  • Validation report
  • Reference standards
  • Samples for evaluation, and
  • Supplies that are difficult to procure

Reference:

http://www.nbchem.de/mediapool/120/1202675/data/110914_AMDVT_bn.pdf

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539

 

Master Production Record (MPR)

A Master Production Record (MPR)is one of the several important documents that a manufacturer of finished pharmaceuticals has to maintain and furnish. It is one of the indispensable parts of pharmaceutical good manufacturing practices (GMP’s). FDA’s regulations on Master Production Record (MPR) are found in Code of Federal Regulations (CFR)’s Title 21, Volume 4. The current standard was revised on April 1, 2012.

Emphasis on double checking

FDA’s Master Production Record (MPR) guidelines are framed with the intention of ensuring that the finished pharmaceutical products maintain the same uniformity across each batch, no matter how many batches are produced of the pharmaceutical product. The manufacturer has to maintain records for each batch and stage of production. These batches have to be prepared, checked and signed by one person designated by the organization. Another independent, second person has to cross check these and carry out the same procedures, namely prepare, check and sign of the first person.

What should the Master Production Record (MPR) contain?

The FDA has clear guidelines on what all should go into the Master Production Record (MPR). It should have these:

  • The product’s name and strength as well as a description of the dosage form
  • The name, weight and measure of each active ingredient
  • Full list of the components that have gone into the drug
  • Aprecisedescription of the weight or measure of each component using the same weight systemfor each component
  • A Master Production Record (MPR) should also have a statement about the excess quantity of any of its components
  • It should also have a statement of theoretical weight or measure that the drug had at different, designated phases of processing
  • A description of the drug product containers
  • The Master Production Record (MPR) should have allspecifications,sampling and testing procedures,manufacturing and control instructions, precautions to be followed and special notations.

Reference:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.186

Contact Detail
GlobalCompliancePanel
webinars@globalcompliancepanel.com
http://www.globalcompliancepanel.com
Phone:800-447-9407
Fax:302-288-6884
43337 Livermore Common | Fremont| CA | USA | 94539