-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
----Discussion on the implementation of process verification based on reasonable compliance
On a feasting night, the author’s mobile phone ticked, and when I took it out, it turned out that a group of friends in a professional group asked: "Can the liquid in the same dispensing tank for oral solution be filled with two? The machine is filled at the same time, and the two filling volumes have different specifications! Can this be done for process verification?"
A certain "brother" expert said no, but my "brother" said yes, so a great battle began, and until the end, my brother was overwhelmed with alcohol and said: "Go to sleep, and send a text tomorrow to pick you
When I got up the next morning, I discovered that at midnight last night, there was another group of friends faintly making a knife: "After a solid oral preparation of an innovative drug is made into a general mixture, the process verification registration application for capsules of different specifications is carried out.
This gentleman specializes @, whose language is lonely, and his feelings are grudges, so that the author who wanted to be lazy feels that I am sorry if I don't write anything
1.
2.
The above two paragraphs are a bit convoluted and incomprehensible.
1.
2.
Please note that the author once wrote an article "I only know compliance, but I don't know it is reasonable" many years ago, you can refer to it
Safety is mainly determined by the impurity and external pollution of the process itself and its own adverse reactions.
We talk about effectiveness
Let me talk about a misunderstanding.
1.
2.
Therefore, the previous example of Youyou tells you that the opinions of CDE or some of the reviewers of CDE are not in agreement
Therefore, it is understandable that CDE has its own concerns for this problem, but the people will be very aggrieved
So let’s digress, whether this kind of recognized pain point problem in the future, we use the platform of non-governmental communication, the official such as CDE can put down the shelf and put some energy (abandon the current official website to reply), and both parties can use the network ID to avoid some Embarrassed, think about it
.
If this can be achieved, it will be a blessing for the industry
.
It is also a good thing for officials.
For example, some rookie reviewers and inspectors can also make rapid progress
.
Back to the topic, the reasons why the author agrees are as follows:
"
The process is composed of processes, which exist alone and in harmony.
In the process verification stage, it is necessary to fully consider how the single rationality of the process can be proven, and also consider the reliability of the quality attributes expressed by the final combination of the overall process
.
Therefore, the process verification must be carried out completely in accordance with the registered process, and it is not advisable to lack the necessary flexibility
.
Even today, when the concept of process life cycle management is vigorously promoted, the process verification at the initial stage must be done in three batches and should not be a heaven
.
"
As follows, I quote an example of a CDE question and answer from a certain "brother", attacking the shield of the son with the spear of the son:
ask:
According to the third paragraph of Article 60 of Appendix 1 of the 2010 version of GMP: "Freeze-dried products are a batch of homogeneous products produced in the same batch of liquid medicine using the same freeze-drying equipment in the same production cycle";
The answer to question 502 of the "2010 GMP Difficult Questions and Answers" compiled by the National Bureau "According to the principle of batch division of sterile drugs in Article 60, terminally sterilized small-volume injections, the same liquid dispensing tank for the final preparation of the drug, If the products produced by two linkage lines are sterilized once in the same sterilizer, the products are regarded as a batch of products.
If the same sterilizer is used for sterilization in batches, the sub-batch number is usually used to sterilize each sterilizer separately.
Check"
.
Excuse me: For freeze-dried powder injection products, can the drug solution in the same dilute preparation tank be filled by two washing-drying-irrigation linkage lines, put into a freeze-drying machine and freeze-dried, and compiled into a product batch number ?"
answer:
"The freeze-dried product is a batch of homogeneous products produced in the same production cycle using the same freeze-drying equipment with the same batch of liquid medicines
.
The high-risk uneven events that may occur in the two filling lines make the level of sterility assurance inconsistent
.
Otherwise, it cannot be filled by two washing-drying-irrigation linkage lines, loaded into a freeze dryer and freeze-dried, and compiled into a product batch number
.
"
Author's comment:
CDE's response showed a clear tendency and a sense of distrust of the company
.
"The high-risk uneven events that may occur between the two filling lines make the level of sterility assurance inconsistent
.
"
This sentence seems reasonable, but it does not conform to the facts.
The basic filling control of domestic filling machines has reached a sufficient level, let alone the management level of the enterprise;
In addition, from the perspective of reverse thinking, how the difference between the two filling lines can lead to high-risk unevenness, then one of them will have a high probability of inter-batch uniformity problems, which is completely another problem
.
So this reply is incorrect
.
But on the other hand, the follow-up sentence "Enterprises should have corresponding measures to ensure that the operating procedures for effective handling of uneven incidents" shows the rationality and tolerance of CDE, but the root cause is still not understanding the current reality of the enterprise
.
If any company can't do this now, it would have been killed by the local bureau long ago
.
Of course, some experts of CDE have reasonable considerations from certain perspectives.
For example, in batches, due to separate packaging, the respective packaging time is shortened, so some risks are not fully exposed or process verification is not sufficient, such as :
The shortening of the oral liquid duration leads to the challenge of solution bioburden and the risk of solution inhomogeneity, and whether the performance of the filling machine is unstable under long-term challenges, but these can be supplemented by other verification data
.
In terms of solids, for capsule dispensing or tablet compression, the possible risk lies in the risk of material stratification caused by the length of time, but in reality, the difference between two hours and eight hours is not as large as imagined
.
For multi-dose formulations, the risk may be greater.
After all, the amount varies greatly, but it is still the same as before.
The stability of the pharmaceutical equipment can be supplemented by other verifications.
There is really no need to waste expensive APIs.
.
Taking a step back, part of the process or individual process verification during the registration batch is insufficient:
One can be partially proved by short-term data, as well as the storage time limit of intermediate products, and the investigation of stratification stability
.
Both, this part of the stability of the loading and the unevenness caused by the delamination can be fully proved by the continuous monitoring plan of the post-marketing process.
No company is unwilling to implement this, and this is also advocated by the concept of continuous process confirmation
.
For the three, after the market changes, batch changes will inevitably become normal.
Naturally, this part of the research needs to be fully studied as the batch expands
.
Afterword:
In fact, for some drugs that are in short supply in three years, two batches may be produced.
In fact, the same is true.
Whether it is production or verification, the batch can be monitored by high-frequency monitoring to ensure the uniformity of the batch.
Why such rigid constraints?