FOI release
new Request for information following your Ref: FOI2025/01247
Case reference FOI2026/00082
Received 26 January 2026
Published 4 March 2026
Request
In your response about safe endotoxin limits, answer 3 you explained "This proposal being discussed was to harmonise the K value for intrathecal and intravenous routes and to introduce a K value for an epidural route." Specialist Pharmcay serivce states https://www.sps.nhs.uk/articles/choosing-an-injectable-medicine-for-intrathecal-administration/ USP Chapter <727> states that “Compounded Sterile Preparations (CSPs) administered epidurally should have the same endotoxin limit as that of intrathecally administered CSPs”. As this aligns with the (unwritten) MHRA expectation that “if tested, epidural solutions would conform to the standards for intrathecals” it would be prudent to adhere to this position. Ther is therefore in place a K value for the epidural route and it tracks the intrathceal route. The SPS page cited explains Endotoxin Limit (EL) = K / M Where K is: • 5 IU/kg of body weight for any parenteral route of administration other than intrathecal, which is the threshold pyrogenic dose of endotoxin per kg of body weight. • 0.2 IU/kg of body weight for intrathecally administered products. Where M is: • the maximum recommended bolus dose of drug per kg of body weight, or • the maximum total dose administered per hour, for injections to be administered at frequent intervals or by continuous infusions For intrathecal administration, the maximum permissible endotoxin dose is 25 x less than for the same product administered via the IV route. This estimate can be used as part of an initial assessment to determine whether an injectable medicine licensed for parenteral use is likely to be suitable for administration by the intrathecal route. 1. as you state the limits are not increasing, please confrim that "harmonise" in your reply means "leveling down" intravenous safe limit to the the current K value used for intrathecal route. 2. If harmonise does not mean leveling down but leveling up , please provide a link to the safety evidence that justifies MHRA policy change for levelling up intrathecal dosing levels to intravenous levels 3. Please provide internal MHRA justification for MHRA altering its "unwritten rule" if the proposed new rule is not to codify the exisitng epidural parity with intrathecal administration 4.. If this harmonisation drive is a general leveling up please explain why it is being promoted specifically in view of well known difficulties and expense invoived of detecting masked endotoxin/ and low endotoxin recovery associated with mRNA and saRNA LNPs cultured in eschrichia coli, and given leveling up i this way manifestly contradicts the fundamental Regulatory "precautionary pronciple", the ethical premise of primum non nocere.
Response
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