Medical Device Sterile Packaging In China (二)

Packaging process verification

For most people involved in packaging related work, "packaging process verification" should be a very strange term, because it is not a theoretical vocabulary, so there is no such term in the textbooks of general universities or vocational and technical schools. To be precise, the word "packaging process" is not mentioned. "Verification" itself should be a typical term in the industrial field. The common industrial fields are IT semiconductor industry, pharmaceutical industry and medical device industry. It can be seen that “validation” is a rigorous term and is therefore used in some industries where process safety and stability are very high. The packaging industry has not always been an industry that is very sensitive to safety or stability, so there are fewer people in the industry who know "validation." However, when the package is considered together with the packaged contents contained therein, the packaged material plays a decisive role in the packaging requirements. The MDSP described in this article is one of the typical ones.

In other words, packaging process validation is essential to achieve CE certification. Of course, this may not be the case. For example, if you have a range of products, you can choose one of the most challenging products, such as the heaviest, the largest, the sharpest, etc., according to the requirements of ISO11607-2006. The packaging process validates the policies and regulations, and then uses a written document describing the rationale for choosing the most challenging product and documenting it as part of the verification report to prove that the series is package-proven.The ISO11607-2006 mentioned above is also a relevant standard for MDSP process validation. It is also the most direct and detailed standard for MDSP process validation. The second part specifies the pre-formed sterile barrier system (PSBS). Manufacturers of Sterile Barrier Systems (SBS) are required to verify the heat seal process necessary for their production. However, it is unfortunate that offset printing, the current domestic medical device packaging suppliers have not systematically verified the heat sealing process necessary for its production process, and the related knowledge and training are also very scarce.Although the above three regulations stipulate the necessity of MDSP process verification, the concepts given by these standards regarding MDSP process verification are still difficult to understand for the average person. Broadly speaking, process validation is interpreted as a documented process that documents and summarizes the factors and information related to the continuous stability of product packaging quality and forms a verification report. According to GHTF (The Global Harmonization Task Force, the Global Medical Device Standards and Regulations Coordination Organization, which is mainly responsible for the unification and coordination of standards and regulations for medical devices in developed countries and regions such as Europe, America, Japan and Australia) The explanation given in the document entitled "Process Validation Guidance" is a solution to ensure continuous and stable process flow, but in the end it is necessary to submit a verification report manufacturer information in a systematic way. There are relevant experimental data to support this report. Of course, this document of GHTF is suitable for many processes used in the production of medical devices, such as sterilization, injection molding, etc., not only for the packaging process, but the FDA also recommends this guidance document as a reference for process validation by medical device manufacturers. .

There is a need to clarify two concepts that are very confusing in the domestic industry, as they involve equivalent translation in Chinese and English. The first one is Verification. The literal translation is the meaning of “confirmation, verification”. It is a concept with a relatively small range and weak strength. It can be used to prove that a design meets the expected requirements with simple data, experiments or drawings. The actual heat seal strength data of the sample proves that it meets the expected range; the second is Validation Network Publishing, which is the “validation” mentioned in this article. It is a wide-ranging concept, including collecting various schemes and evidences. And data to demonstrate the continuous stability of the packaging process.

It can be seen from the above that in addition to the necessary information and other layout design, the rest of the content is related to the three necessary components of the MDSP process verification, IQ, OQ and PQ. The following three concepts are highlighted respectively. . The label is first IQ, which requires that the equipment be properly installed at the right place, including whether there is enough operating space, whether the auxiliary facilities such as water and electricity are complete, whether the equipment parameters are calibrated, and whether the equipment has a response to the production environment. The ability to parameter fluctuations and how this capability is performed, whether the software related to the device has been verified, whether the equipment operator has been trained, whether the various drawings and instructions for the equipment are complete, etc., can list the information required above. Fill in the digital printing and finishing, and check whether it has been completed item by item. If all is completed, the IQ is completed. The equipment parameter verification information table and the operation staff training table need to be given in the form of an appendix after the IQ part.

Next is OQ, which requires finding a parameter interval that can continuously and stably produce a product that meets the intended target (please note that the parameter interval is emphasized, not just a parameter point). Packaging logistics is the core of verification and also due to product Or a project with different process equipment and more content changes. The approximate parameter range of the OQ can be initially determined, and this preliminary determination can be based on the basic characteristics of the material, past work experience, and valid empirical historical data. Next, we need to design an experimental scheme to confirm the validity of this initially determined parameter range. The process of this design experiment is usually called the DOE (Design of Experiment) process flow. There are many specific experimental schemes, which are based on different packaging. Design and heat-sealing equipment to determine, of course, MDSP packaging quality acceptance criteria and project testing methods are also defined in this OQ.

It is worth noting that the MDSP packaging quality acceptance standard is generally self-defined by the enterprise, because the existing packaging details are still lacking in the universal applicability of the beiren shares, so the general packaging acceptance criteria are based on the enterprise self-standard, open standards. For reference only. Finally, samples are made according to the DOE and the relevant packaging items are tested according to the specified testing methods. The conventional items are package integrity, packaging protection, clean opening and packaging appearance, etc. The clean opening characteristics are not very good in China. The factors that are valued and subjective judgment are very large, but for the instruments used in the operating room, this is a very important test indicator. The US market is particularly strict with this indicator. If the results of all test items reach the predetermined target value, then the parameter interval is regarded as the verified parameter interval; if the predetermined requirement cannot be fully met, the parameter may be fine-tuned. Of course, the actual implementation may be more skillful. In short, the rich experience and familiarity with the materials are very helpful in quickly finding the best process parameter interval in OQ, which is also a kind of experience and knowledge saving in process development. Reflecting color management, because according to statistics, a complete process verification is very expensive.

It is necessary to determine the parameter interval in OQ instead of just a parameter point, because for the general packaging equipment, such as automatic forming-filling-heat sealing machine and ordinary heat sealing machine, the temperature of the heat sealing mold and the air compressor supply are Air pressure is a highly prone to fluctuation in the normal production process. If only a parameter point is given instead of an interval, once the parameter fluctuations that must occur in this normal production exceed the actually acceptable range, Unqualified products will appear. In theory, the parameters should be considered as an interval rather than a point, but the size of the interval is different from the manufacturer information, and when the interval is very small, it is close to a point. During production, the parameter should be set at the midpoint of the parameter interval, so that when there is parameter fluctuation, it can also have a certain tolerance space; if this point is selected in the upper or lower limit of the parameter interval, even if the parameter has slight fluctuation, it will cause quality. Stability issue.

Finally, the PQ layout design requires that this selected parameter space be consistently and consistently produced in a large-scale production. Of course, PQ is more like a project related to product quality stability control, has little relevance to the engineering and technical department, and is relatively easy to understand and implement. The usual practice is to sample the first three batches of products according to the predetermined sample size and acceptance level (AQL) at the beginning of continuous production. According to the test items and test methods in OQ, the relevant sample test is over-packaged and combined with detection. The data is used to derive a PQ report and use this as a basis for determining whether the entire packaging verification process is finalized.

After fully understanding the core IQ, OQ and PQ of the MDSP process verification and designing a qualified verification scheme, the personnel of the production and technical departments can complete the inspection and confirmation of the equipment and the process parameter interval according to the requirements in the verification scheme. The establishment, initial confirmation of the continuous quality stability of the three production batches, and the quality department personnel are responsible for the detection of relevant data and feedback to the front-end color management. If everything meets the expected requirements, then these will be obtained. The parameter information and experimental data are filled into the verification scheme to form a final MDSP process validation report.

The MDSP process validation report thus obtained is a complete written report of a series of rigorous testing procedures and a strong reason for our confidence in the continuous stability of the product packaging quality.

It is worth pointing out that because there is no fixed mode certification for packaging verification, there are no very credible companies or organizations that have given detailed template templates. (The author has read many packaging verification solutions for large European and American companies, each company or everyone. The solutions are different, and some are not very standardized. In order to standardize the work of packaging verification, each medical device manufacturer or its packaging supplier should have a template for their own packaging verification program Manroland to regulate The company's work in packaging verification and unified reporting mode. Of course, different products may have different considerations in the inspection project, but they are very close in the IQ and PQ fields and the OE part of the DOE, so the template still has some versatility.At present, the packaging process verification is only applied to the digital printing machine in the MDSP field. However, based on the deep understanding of the packaging industry, the author believes that because food and pharmaceutical packaging are also closely related to the health of consumers, their packaging design is also very much needed. Packaging process validation to confirm the continuous stability of the product packaging; the packaging protection and safety requirements of daily chemical and personal hygiene products are slightly lower than the above products, but if necessary, packaging verification; general industrial products and The packaging process of consumer electronics products is too simple and high-fidelity printing, or low degree of automation (of course, some foreign automated packaging equipment is also very advanced), the requirements for package integrity or sealing are not very strict, and Emphasis is placed on buffer-protective packaging during transport and circulation, thus essentially eliminating the need for very rigorous and complex packaging verification procedures.

In general, packaging process verification is an engineering methodological problem. Its implementation does not involve the essence of product packaging design, but it has positive help for the continuous stability of product packaging quality, so it is worth our visit. practice.

Finally, I would like to clarify the issues of packaging verification and packaging quality inspection. Although they are related to the safety of product packaging Fuji Starlight, there are still differences in depth between the two. Packaging Verification is a complete packaging process quality stability assurance program that itself contains the necessary description of the product packaging quality testing lab design and acceptance criteria, and requires that these testing protocols and results be included in the final packaging validation report. That is to say, the package quality inspection is only a small part of the package verification; and the final purpose of the package quality inspection is to detect whether the product package produced in the verified process parameter interval meets the target requirements set. After all, the difference between the two is the difference between the validation of the product packaging (Validation) and the verification (Verification).

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