Australian public assessment for Albumin (human)
VI. Overall conclusion and risk/benefit assessment
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- Bu səhifədəki naviqasiya:
- External clinical expert 1
- External clinical expert 2
- Quality The quality evaluator recommended approval, but with batch release conditions of registration. Nonclinical
- Albumin or plasma protein fraction
- Implications for practice
- Delegate’s considerations
- Registration of both 20% and 25% concentrations
- Mixing of Albumex and Albunate in the one infusion or one-episode-of-care
- Conditions of registration
- Proposed action The Delegate had no reason to say, at this time, that Albunate should not be approved for registration. Request for ACPM advice
- Request for ACPM’s advice
- Biological chemistry evaluation
- Nonclinical evaluation As stated, it was agreed at a pre-submission meeting that a nonclinical evaluation was not required. Clinical evaluation
- Risk Management Plan CSL has no comment on the RMP evaluation. Discussion
- Advisory committee considerations
- Proposed conditions of registration
- Points of clarification for sponsor post ACPM from the delegate
- Post ACPM response from sponsor
- Delegate’s review of the response
- Specific conditions of registration applying to these goods
- Attachment 1. Product Information
- Attachment 2. Extract from the Clinical Evaluation Report
VI. Overall conclusion and risk/benefit assessmentThe submission was summarised in the following Delegate’s overview and recommendations. IntroductionUse of albumin in clinical practice in AustraliaRandomised studies have not convincingly shown a benefit of colloids (such as albumin) over crystalloids in critically ill patients on the outcome of mortality (see results of Cochrane review below). Anecdotal evidence suggests that there is wide variation in the use of albumin across hospitals in Australia, with no particular pattern to the variation. The TGA therefore sought the views of two external clinical experts on the use of albumin in Australia. The following responses were provided: External clinical expert 1
Caironi P, et al ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-1421. Suarez JI, et al. Human albumin administration in subarachnoid haemorrhage: results of an international survey. Neurocrit Care. 2014;20:277-286. Suarez JI, and Martin RH. Treatment of subarachnoid haemorrhage with human albumin: ALISAH study. Rationale and design. Neurocrit Care. 2010;13:263–277. ALISAH II, a Phase III, randomised, placebo-controlled trial to test the efficacy of albumin, is underway. Without much data 20% albumin is often used as a slow infusion to boost low albumin levels, to promote diuresis with the help furosemide or as a colloid backup during dialysis to allow better volume expansion whilst removing fluid.
Albumex 20% is used to restore plasma oncotic pressure in patients with ascites (following an ascitic tap). The two clinical experts were also asked about the implications of an albumin shortage in Australia: External clinical expert 1This happened for a short period a couple of years ago and there were very dissatisfied local clinicians. Nevertheless many places/countries hardly allow albumin administration due to its expense. External clinical expert 2There is an absolute need for albumin solutions in situations 1, outlined above (under advice from external clinical expert 2). There is a strong indication for their use in situations 2 and 4. For situation 3, albumin solutions have a probable benefit in uncommon but life threatening scenarios, typically in shock states in which there is some concern about overuse of other colloids (Gelofusin, Voluven). In many of these scenarios other IV fluids can be used, but it may not be ideal. There is a possible (but theoretical) risk of avoidable patient harm. QualityThe quality evaluator recommended approval, but with batch release conditions of registration. NonclinicalIt was agreed, pre-submission, that a nonclinical evaluation was not required, as long as the nonclinical aspects of the proposed Australian PI for the Swiss manufactured Albunate were the same as those for the already registered Australian manufactured Albumex. Albumin is unlikely to have toxicological effects on humans because it is of human origin. ClinicalThis was a literature based submission (an approach approved by the TGA pre-submission) that comprised: randomised controlled trials (RCTs) and meta analyses around the efficacy of albumin generally pharmacovigilance data collected from periodic safety activities from 1996 to the present, specifically for Albunate a small post-marketing safety study of Albunate (marketed as Albumin SRK), from Austria. Albunate was registered in Europe (through national licenses) and the US as a “well established use” product. There were no sponsor initiated trials. The clinical evaluator noted that there was no direct comparison between Albunate and Albumex, but also noted that “there was global clinical practice usage data to suggest that as a HAS, Albunate is effective and safe for intravenous infusions for the indication of restoring and maintaining volume.” The clinical evaluator recommended that, “ … the 5% concentration be registered in keeping in line with the SAFE study and one of the hyperoncotic concentrations; for consistency with Albumex suggest the 20% concentration.” The sponsor has replied that both the 20% and 25% strengths should be registered so that in the event of a shortage there is “flexibility to respond as quickly as possible with either registered product, depending on stock availability”. EfficacyHuman albumin, as a therapeutic agent, was developed 60 years ago. In the 1980’s and 1990’s, several authoritative bodies considered recommendations for appropriate use. Broadly speaking, the consensus was that administration of albumin was probably justified in cases of acute circulatory problems caused by hypovolemia. Since then, further evidence has accumulated and there have been questions about whether albumin (and colloids in general) was any more efficacious than crystalloids. The accumulated evidence on the outcome of mortality was meta-analysed in a Cochrane systematic review; some excerpts are given below.17 Albumin or plasma protein fractionTwenty-four trials reported data on mortality, including a total of 9,920 patients. The pooled relative risk (RR) was 1.01 (95% CI 0.93 to 1.10). When trials by Boldt were removed, the results were unchanged (RR 1.01; 95%CI 0.93 to 1.10). When we excluded the trial with poor quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09). Comment: Some of the trials would have included the Swiss manufactured Albunate, but it is not possible to identify which ones. 80% of the weight towards the pooled estimates in the meta-analysis came from the SAFE study, conducted in Australia and New Zealand. That study used the Australian manufactured Albumex (4.0%). Hydroxyethyl starchTwenty-five trials compared hydroxyethyl starch with crystalloids, including a total of 9,147 randomised patients. The pooled RR for mortality was 1.10 (95% CI 1.02 to 1.19). When trials by Boldt were removed, the results were unchanged. Modified gelatinEleven trials compared modified gelatin with crystalloid, including a total of 506 randomised patients. The pooled RR for mortality was 0.91 (95% CI 0.49 to 1.72). When trials by Boldt were removed, the results were unchanged. DextranNine trials compared dextran with a crystalloid, including a total of 834 randomised patients. The pooled RR for mortality was 1.24 (95% CI 0.94 to 1.65). Implications for practiceThere is no evidence from randomised controlled trials that resuscitation using colloids compared with crystalloids reduces the risk of death in patients with trauma, burns or following surgery. The use of hydroxyethyl starch might even increase mortality. Since colloid use is not associated with improved survival and colloids are considerably more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified. SafetyAntibody reactions against albumin associated, still unidentified antigens, may occur. This is manifested by fever, urticaria and nausea. These symptoms typically disappear if the infusion rate is decreased or if the infusion is stopped. Severe anaphylaxis and shock can occur; it is exceedingly rare. Circulatory overload may develop as a non-specific volume effect if albumin is administered in too large quantities or too rapidly relative to the needs of the individual patient. Virus validation studies have demonstrated that viruses are eliminated by at least two different mechanisms during manufacture. There are no documented cases of transmissions of viruses or other infectious agents by albumin solutions. In 1996, four ADRs (transient hypotension during major surgery) were reported after the treatment with one batch of Human albumin "SRK", former name of Human albumin "ZLB" (that is, Swiss manufactured Albunate that is the subject of this submission). The batch withdrawn by the manufacturer from the US market after batch analysis showed an increased activity of the prekallikrein activator (PKA). It was shown that the increase occurred after batch release during the storage; and, although never proven, the increase was considered a possible reason for the ADRs. Therefore the manufacturer identified critical steps in the production and introduced specific measures to prevent an elevation of PKA activity during shelf life. In Austria the manufacturer was instructed by the authorities to perform studies on PKA activity during the storage. The results submitted did not show an increase of PKA during shelf life. A non-randomised, post-marketing study (prospective, no control group) was conducted in Austria (n = 211). The participants were critically ill surgical patients. Either Albunate 5% or 20% was administered for volume replacement or correction of an oncotic deficit. Five patients died because serious preceding traumatic injuries, 11 patients showed slight to moderate hypotension, 9 patients showed light or moderate erythema. No case of severe anaphylactic reaction and no other undesirable effects were observed. Inferences from the study were limited because there was no control group; and also because of the small sample size. Risk management planSummary of safety concerns Table 4: Summary of ongoing safety concerns including the mitigation strategy
The two external clinical experts were asked whether any measures beyond routine pharmacovigilance were required. They both stated routine pharmacovigilance was adequate. Risk-benefit analysisDelegate’s considerationsEfficacy and safetyThis Swiss manufactured albumin (Albunate) has been marketed in several countries (with regulatory systems similar to Australia) for about four decades. The proposed registration is to ensure a continuous supply of albumin in Australia. [Information redacted]. There are no sponsor initiated trials for Albunate. The product has been approved in all markets based on literature submissions; or initially as an “established use” product. Albumin is a biologically derived product. However, the sponsor is not making any claim that Albunate is a biosimilar of Albumex. Instead, the sponsor is seeking registration of Albunate as a stand-alone product. Literature based evidence for the efficacy of albumin is patchy, with some experts arguing that, for hypovolaemia, crystalloids might be just as effective. The TGA sought the views of two external clinical experts who advised that albumin currently has an established place in Australian clinical practice; as it does globally. In terms of safety, mild reactions such as flush, urticaria, fever and nausea occur rarely. These reactions normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped. Even more rarely, severe reactions such as anaphylaxis may occur. No cases of virus transmission with human albumin manufactured to European Pharmacopeia standards have been reported. In the responses to questions raised by the TGA the sponsor confirmed that Albunate will be registered but not supplied unless there is a shortage of albumin. Registration of both 20% and 25% concentrationsBoth the external clinical experts advised that only one of the 20% or 25% concentrations is needed. The sponsor agreed that there was no clinical need to have both strengths registered. However, the sponsor, still wanted to register both the 20% and 25% strengths in the event of a shortage, so that there is “flexibility to respond as quickly as possible with either registered product, depending on stock availability”. Mixing of Albumex and Albunate in the one infusion or one-episode-of-careThe sponsor provided the following response: “[information redacted] There could be an overlapping period when both products are on the market at the same time. However both Human Albumin solutions should not be mixed in the same infusion. As indicated in the labelling, Albunate should not be mixed with other products: “Human albumin must not be mixed with other medicinal products, whole blood and packed red cells.” The simultaneous presence of several different Human Albumin solutions on the same market is very common. For many years CSL Behring has marketed different Human Albumin solutions at the same time in the same countries for example US, Europe and China. Besides, several other Human Albumin solutions from different companies are also marketed worldwide. No safety concern has been raised concerning the presence of different Human Albumin solution products on the market simultaneously. Both Albunate and Albumex comply with the European Pharmacopoeia (Ph. Eur.) requirements for ‘Human Albumin Solution’. As per the Ph. Eur., Human Albumin solution may contain excipients such as sodium caprylate (sodium octanoate) or N acetyltryptophan or a combination of the two. Albunate and Albumex differ in the stabilisers added to formulate a parenteral solution. Albumex contains 32 mmol/L sodium octanoate whereas Albunate contains 16 mmol/L sodium octanoate and 16 mmol/L sodium N-acetyltryptophanate. Should both formulations be administered to a patient in a single day, the relative proportion of N-acetyltryptophanate would be between 0% (Albumex only) and 50% (Albunate only). The relative merits of these stabilisers have been examined. No safety concern arises from the relative proportion of N acetyltryptophanate, should mixing occur. [Information redacted] CSL Behring provides the assurance that an appropriate logistical and communication plan developed and executed in conjunction with the NBA and Australian Red Cross Blood Service (ARCBS) will be in place.
The quality evaluator has specified the following Conditions of Registration: Batch Release Testing by the TGA’s Office of Laboratories and Scientific Services (OLSS) It is a condition of registration that, as a minimum, the first five independent batches of Albunate 5 (50 g/L (5% w/v) 250 mL) Albunate 5 (50 g/L (5% w/v) 500 mL) Albunate 20 (200 g/L (20% w/v) 50 mL) Albunate 20 (200 g/L (20% w/v) 100 mL) Albunate 25 (250 g/L (25% w/v) 50 mL) Albunate 25 (250 g/L (25% w/v) 100 mL imported into Australia are not released for sale until samples and/or the manufacturer’s release data have been assessed and endorsed for release by the TGA. The sponsor should supply: Certificates of Analysis of all active ingredient (drug substance) and final product. Information on the number of units to be released in Australia with accompanying expiry dates for the product and diluents (if included). Evidence of the maintenance of registered storage conditions during transport to Australia.
Question for sponsor[Information redacted] the possibility of one patient receiving a mix of Albumex and Albunate in the one infusion what safety risk this may pose how any risk should be mitigated.
Summary of issue/sAlbunate has been registered and marketed in several countries for four decades. This is a literature based submission. Albumin has been registered as a “well established use” product. There are no company sponsored, clinical endpoint studies. [information redacted] Literature based evidence for the efficacy of albumin versus crystalloids is patchy, with some experts arguing that, for hypovolaemia, crystalloids might be just as effective. Albumin currently has an established place in Australian clinical practice; as it does globally. In terms of safety, mild reactions such as flush, urticaria, fever and nausea occur rarely. These reactions normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped. Even more rarely, severe reactions such as anaphylaxis may occur. No cases of virus transmission with human albumin manufactured to European Pharmacopeia standards have been reported. Proposed actionThe Delegate had no reason to say, at this time, that Albunate should not be approved for registration. Request for ACPM adviceThe ACPM is asked to advise on whether efficacy and safety have been satisfactorily established. Response from sponsorRequest for ACPM’s adviceCSL welcomes the Delegate’s comment in the Pre ACPM preliminary assessment: “I have no reason to say, at this time, that Albunate should not be approved for registration”. Background (including overseas regulatory history)The background to the product is accurate. [Information redacted] There is currently no alternative albumin product available on the Australian market. CSL acknowledges the views of the two external clinical experts detailed ‘Use of albumin in clinical practice in Australia’. The overview/regulatory history as provided is accurate and correctly reflects that Albunate (with different trade names) has been in clinical use for nearly 40 years and is approved in Switzerland, the USA, the EU, Canada and a number of other Asian and Middle Eastern countries.
Nonclinical evaluationAs stated, it was agreed at a pre-submission meeting that a nonclinical evaluation was not required. Clinical evaluationThe summary of clinical evaluation of the literature based submission provided in the Delegate’s request accurately reflects the clinical status of Albunate. CSL notes the clinical evaluator recommendation that the 5% concentration be registered in line with the SAFE study and one of the hyperoncotic concentrations. CSL reiterates the desire to register both hyperoncotic strengths of Albunate, 20% and 25%, so that there is flexibility with either presentation, depending on stock availability. The summary of clinical efficacy provided in the Delegate’s request accurately reflects the published studies regarding the clinical efficacy of Human albumin. The summary of clinical safety provided in the Delegate’s request accurately reflects the clinical safety status of Albunate. Risk Management PlanCSL has no comment on the RMP evaluation. DiscussionCSL welcomes the views of the two external clinical experts who advised that albumin currently has an established place in Australian clinical practice. [Information redacted] Conditions of registrationCSL confirms that an updated RMP (version 3.0) has been provided to the RMP team. CSL has noted the condition to provide samples from the first five independent batches of Albunate imported into Australia for assessment and endorsement by the TGA OLSS prior to release to the market. Question for sponsorThe NBA manages and coordinates arrangements for the supply of blood and blood products on behalf of the Australian Government and state and territory governments. Part of their role is to assess blood supply risk and engage in contingency planning. The NBA is not in a position to provide a statement of product risk management as this is outside their jurisdiction. Therefore, CSL will not be providing a statement from the NBA as part of this response. The issues around risk of mixing of Albumex and Albunate in the one infusion or one episode of care have already been addressed in the response provided to the first round clinical evaluation and provided within the Request for ACPM’s Advice document. Additionally, as requested in review of the PI, the proposed PI has been updated to include a statement that Albunate must not be mixed with other albumins. Advisory committee considerationsThe Advisory Committee on Prescription Medicines (ACPM), having considered the evaluations and the Delegate’s overview, as well as the sponsor’s response to these documents, advised the following: The ACPM, taking into account the submitted evidence of efficacy, safety and quality, agreed with the Delegate and considered Albunate solution for intravenous infusion vial containing 50 g/L (5% w/v) and 200 g/L (20% w/v) of albumin to have an overall positive benefit–risk profile for the indication; Restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated and use of a colloid is appropriate. The choice of albumin rather than artificial colloid will depend on the clinical situation of the individual patient. The ACPM recommended that Albunate 25 solution for intravenous infusion vial containing 250 g/L (25% w/v) (250 mL and 500 mL) of albumin should not be approved for registration. In making this recommendation, the ACPM was concerned about confusion between the 25% and 20% solution. This should be clarified with the sponsor.
Proposed Product Information (PI)/Consumer Medicine Information (CMI) amendmentsThe ACPM agreed with the delegate to the proposed amendments to the PI and CMI and specifically advised on the following: Clarify with the sponsor that the Indication is based on the EMA recommendations and, in particular, why plasma exchange is not listed as an indication when it is mentioned in the dosing instructions. Consideration could also be given to clarifying the text under DOSAGE and ADMINISTRATION - Compatibility with other fluids.
Specific adviceThe ACPM advised the following in response to the delegate’s specific questions on this submission: Advise on whether efficacy and safety have been satisfactorily established. The ACPM advised that efficacy and safety have been established satisfactorily for the 5% and 20% strength. The ACPM advised that implementation by the sponsor of the recommendations outlined above to the satisfaction of the TGA, in addition to the evidence of efficacy and safety provided would support the safe and effective use of these products.
Both the external clinical experts advised that only one of the 20% or 25% concentrations is needed. The sponsor agreed that there was no clinical need to have both strengths registered. However, the sponsor, still wanted to register both the 20% and 25% strengths in the event of a shortage, so that there is “flexibility to respond as quickly as possible with either registered product, depending on stock availability”. The ACPM was concerned that having both strengths registered could cause confusion. Can the sponsor clarify whether both the 20% and 25% strengths will be on the market at the same time or whether only one will be available, depending on stock availability? Also, if the 25% is provided, will the ‘dear health care provider letter’ (DHCPL) explain that Ablunate25% is more hyper-oncotic than the Albumex20% and therefore carries an increased risk of fluid overload. Plasma exchange The ACPM noted that plasma exchange is not included in the indication, but is included in the Dosing and Administration and the Posology/Dosing in the Core EU SmPC, as per EMA’s “Guideline on the Core SPC for Human Albumin Solution (CPMP/PhVWP/BPWG/2231/99 rev.2)”. The sponsor is asked to clarify. Compatibility with other fluids Albunate must not be mixed with other medicinal products, whole blood, packed cells or other albumins. The ACPM was concerned that “other medicinal products” could be taken to include saline. Under ADMINISTRATION, the proposed PI (based on the EU SPC) states: Albunate 20 can be directly administered by the intravenous route, or it can also be diluted in a suitable crystalloid solution. The sponsor is asked to clarify. Interactions with other medicines The Albumex PI includes the following: Hypotension has been reported in patients given albumin who are on Angiotensin Converting Enzyme (ACE) inhibitors. This is not in the EU SPC. The sponsor is asked to clarify. Post ACPM response from sponsor
CSL response: [Information redacted] CSL plans to make available only one of the hyper-oncotic strengths at a given time, preferably the 20%. Only in the event of a shortage, would the 25% be supplied instead .There is a theoretical concern that the oncotic pressure of albumin may lead to volume overload, particularly in patients who have underlying risk factors. However, the osmolality is 258 mOsm/kg for both Albumin 20% and Albumin 25%. While there is a 50 g/L difference between the formulations, the colloid-osmotic effect of 200 to 250 g/L is not significantly different, and is approximately four times that of blood plasma. A comprehensive search of the CSL Behring Global Safety Database for all Albumin cases (including Albumin 5%, 20%, and 25%) utilising Medical dictionary for regulatory affairs (MedDRA) and the MSSO SMQ18 haemodynamic oedema, effusions and fluid overload was performed and presented in the last submitted Albumin 5%, 20%, and 25% EU-RMP version 3.1, dated 15 December 2014. Cumulatively from 18 September 1996 to 1 September 2013, nine case reports, the majority of which were hypersensitivity reactions, were identified. Of these 9 reports, there were 3 reports that occurred in patients with the preferred term (PT) Cardiac failure congestive and the PT Pulmonary oedema. One patient had congestive heart failure as an underlying condition and was treated for myasthenia gravis with plasma exchange using Albumin 5%. After the third plasma exchange, the patient died at home due to congestive heart failure exacerbation, which was reported to be not related to the plasma exchange procedure or albumin. The remaining two patients reported pulmonary oedema after receiving Albumin 25%. One of these 2 patients received the concomitant medication Terlipressin, the other patient received massive transfusions of blood products, and both had renal impairment which could provide additional plausible explanations for the pulmonary oedema. There were no reports of hypervolaemia in patients receiving Albumin 20%. There is no available spontaneous data that would provide additional information regarding the risk of hypervolaemia in patients receiving Albumin 20% versus Albumin 25% and the overall reporting frequency of hypervolaemia is very rare. CSL proposes that the PI is sufficient for the primary risk minimisation strategy regarding the potential risk of hypervolaemia and haemodilution in high risk patients. The PI for both Albumin 20% and Albumin 25% address the risk of hypervolaemia in specific patient populations, the need for adequate hydration, the need for crystalloid solution in dehydrated patients, and adjustment of dose and infusion rates to the patients circulatory condition as follows: Albunate 20% and 25% proposed PI Albumin should be used with caution in conditions where hypervolaemia and its consequences or haemodilution could represent a special risk for the patient. Examples of such conditions are: decompensated cardiac insufficiency hypertension oesophageal varices pulmonary oedema haemorrhagic diathesis severe anaemia renal and post-renal anuria. The colloid-osmotic effect of human albumin 250 g/L (for Albunate 25 and 200g/L for Albunate 20) is approximately four times that of blood plasma. Therefore, when concentrated albumin is administered, care must be taken to assure adequate hydration of the patient. Patients should be monitored carefully to guard against circulatory overload and hyperhydration. As aligned with the most recently approved Albumin EU RMP v.3.1, no additional risk minimisation is proposed, as providers should be skilled in the use of albumin in patients at risk for volume shifts. Lastly, the same level of rigorous monitoring and management is clearly addressed in the warnings for all formulations of albumin, including albumin 5%. Based on the above, CSL does not believe an extra statement regarding risk of fluid overload in the DHCPL is required. Plasma exchange CSL response: Plasma exchange is a common therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. Through the bulk removal and replacement of plasma pathologic substances such as pathologic Abs, immune complexes, and cytokines can be removed. Plasma exchange leads to a volume deficit and albumin is a common replacement fluid for therapeutic plasma exchange. As albumin is used to restore a volume deficit this is covered by the indication: Restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated and use of a colloid is appropriate. This is in line with the Core EU SPC, as per EMA’s Guideline.19 Compatibility with other fluids CSL response: The information provided in the ‘compatibility with other fluids’ section is general guidance whilst the wording in the ‘administration’ section is very specific and provides detailed instruction on dilution with a suitable crystalloid solution. CSL believes that these two sections do not contradict.
CSL response: This statement is not in the EU SPC and CSL does not have any company information to support including it in the Albunate PI. This interaction has been in the Albumex PI since 1995 and was relevant to previous generations of albumin manufactured in Australia by CSL, namely Stable Plasma Protein Solution (SPPS) and Normal Serum Albumin (NSA). Even though the albumin product manufactured in Australia by CSL has evolved into a much purer product with a significantly lower incidence of ADRs (refer to Che et al. 200620) this statement has remained in the Albumex PI. Delegate’s review of the responseAs a result of a review of the information provided by the sponsor in their post ACPM response the Delegate decided to approve all products applied for in this submission; Albunate 5, Albunate 20 and Albunate 25. OutcomeBased on a review of quality, safety and efficacy, TGA approved the registration of Albunate 5 human albumin 50 g/L (5% w/v) Albunate 20 human albumin 200 g/L (20% w/v) and Albunate 25 human albumin 250 g/L (25% w/v) solution for intravenous infusion, indicated for: Restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated und use of a colloid is appropriate The choice of albumin rather than artificial colloid will depend on the clinical situation of individual patient Specific conditions of registration applying to these goodsThe Albunate (human albumin) EU Risk Management Plan (RMP), Version 3.1, dated 15 December 2014, as qualified by the Australian Specific Annex, Version 3.0, dated May 2015, and any subsequent revisions, as agreed with the TCA will be implemented in Australia. Batch Release Testing. As a minimum, the first five independent batches of Albunate 5 (human albumin 50 g/L (5% w/v) 250 mL) Albunate 5 (human albumin 50 g/L (5% w/v) 500 mL) Albunate 20 (human albumin 200 g/L (20% w/v) 50 mL) Albunate 20 (human albumin 200 g/L (20% w/v) 100 mL Albunate 25 (human albumin 250 g/L (25% w/v) 50 mL) Albunate 25 (human albumin 250 g/L (25% w/v) 100 mL imported into Australia are not released for sale until samples and/or the manufacturer's release data have been assessed and endorsed for release by the TGA Laboratories Branch.
Email: info@tga.gov.au Phone: 1800 020 653 Fax: 02 6232 8605 |